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About me

I am associate professor of Pharmacology (2009), currently working as senior researcher and leader of my own research group at the division of clinical pharmacology, Department of laboratory Medicine, Karolinska Institutet. My research is on global health pharmacology including maternal and child health in Sub Saharan Africa, where the disease burden is paramount and yet little is known about the impact of host-genetic factors, drug interactions, coinfections and comorbidity, and nutrition on both the safety and efficacy of therapy. I have conducted several prospective observational studies, randomized clinical trials, drug interaction and dose optimization studies focusing on major public health problems including treatment of the three most deadly infectious diseases (HIV/AIDS, tuberculosis, and malaria), neglected tropical diseases and antimicrobial resistance that claim millions of lives worldwide, especially in low-income countries. I have conducted several pharmacogenetics, pharmacokinetics, pharmacodynamics and drug interaction studies, biomarker discovery and validation studies for drug-induced liver injury, antimicrobial resistance and Hospital-acquired infections; pharmacovigilance and postmarking surveillance involving mass drug administration and immunization in resource-limited countries.

I have recived several national and international external research grants in competition as a principal investigator.  My research projects and external funding has created opportunities for 10 completed and 3 ongoing PhD students at Karolinska Institutet, and > 95 original research publications in peer-reviewed scientific journals.

Currently I am member of the scientific advisory board for EDCTP, and member of the committee for development research at the Swedish research council.

             

Education

  •  Five year  postdoctoral training in clinical pharmacology, Karolinska Institutet
  •  PhD degree in molecular genetics (2003) from Karolinska Institutet.
  • MSc degree in biochemistry (1996), and Bachelor of pharmacy (1987) from Addis Ababa University, Ethiopia.

 

 

Research description

Project 1:  Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa- PROFORMA (http://proforma.ki.se/).

In sub Saharan Africa, access to medicine including new drugs, vaccines, microbicides for treatment of poverty-related diseases (PRD) is increasing. However, capacities of the National Medicine Regulatory Authorities (NMRAs) to monitor the quality and public safety of new drugs and interventions is not coping with, partly due to shortage of qualified personnel and limited resources. PRORFORMA aims to strengthen the national pharmacovigilance infrastructure and post-marketing surveillance system in Ethiopia, Kenya, Tanzania, and Rwanda by forging partnerships with local academic institutions (training-of-the-trainers for sustainable training programs), national medicine regulatory authorities (practical training to change policy into practice) and public health programs. We aim to generate a cohort of pharmacovigilance-trained human resources from all stockholders including patients, healthcare providers, regulatory staffs that are engaged in pharmacovigilance data collection, analysis, interpretation and data sharing. Our specific objective to strengthen pharmacovigilance and post-marketing surveillance system focusing on public health programs involving mass drug administration for neglected tropical diseases and mass immunization programs. Twelve postgraduates will be trained to serves as part of the future PV expert regional task force in East Africa aligned with the large-scale African medicine regulatory harmonization and WHO’s Pharmacovigilance program.

PROFORMA project is funded by European Union’s Framework Programme for Research and Innovation Horizon 2020 via the European and Developing Countries Clinical Trials Partnership Association (EDCTP2), with co-funding from Sida.

Project 2: Effectiveness dihydroartemisinin -piperaquine versus sulfadoxine-pyrimethamine for prevention of falciparum malaria infection during pregnancy in Tanzania.

Intermittent Preventive Treatment in pregnancy (IPTp) with Sulfadoxine/Pyrimethamine (SP) is the current chemoprophylaxis intervention recommended by WHO for malaria prevention in pregnancy. However, the high prevalence Sulfadoxin/Pyrimethamine (SP) resistance in high malaria endemic areas including Tanzania are likely to undermine the use of IPTp-SP in improving birth outcomes. We investigate whether the combination of dihydroartemisinin-piperaquine (DHP) is superior to SP and co-trimoxazole alone for prevention of malaria in pregnancy among HIV negative and HIV positive pregnant women respectively. The study design is an open-label, two-arm, prospective randomized controlled trial. HIV negative pregnant women are randomized to receive either IPTp-SP or IPTp-DHP. In parallel, HIV positive pregnant women are randomized to receive either co-trimoxazole (CTX) with DHP (IPTp-DHP+CMX) or CTX alone. Result from this study will establish if DHP can be a suitable alternative to replace SP for IPTp for malaria prevention in HIV negative pregnant women, and addition of DHP to daily cotrimoxazole is significant in preventing malaria among HIV positive pregnant women.

This study is funded by grant from Sida.

 

Project 3: Randomized clinical trial to determine effectiveness the efficacy and safety of Praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for the treatment of schistosomiasis in Tanzania.

Neglected tropical diseases (NTDs) such as schistosomiasis remain a burden in Sub-Saharan Africa (SSA), creating a public health concern. NTDs are linked to almost all Millennium development goals (MDGs); and their control is associated with direct impact on the achievement of the MDGs such as reduction of poverty and education. Prevalence of schistosomiasis remains high in SSA, affecting more than 200 million people worldwide, of which more than 80% found in the SSA. Despite the use of praziquantel (PZQ) for mass treatment and disease control, the prevalence of schistosomiasis remains high in some endemic settings. PZQ is effective against mature schistosoma species but has low efficacy against immature schistosomes (juvenile schistosomes). Previous studies report that artemisinin and its derivatives are effective against immature schistosomes. In a randomized clinical trial, we are investigating the efficacy and safety of praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for the treatment of schistosomiasis. Our hypothesis is PZQ plus dihydroartemisinin-piperaquine (DHP) will improve schistosomiasis treatment outcome by covering both matured and immature forms of a parasite and eventually control of the disease achieved.

This study is funded by grant from Sida.

Project 4: Factors affecting malaria treatment outcome among pregnant women treated with artemether-lumefantrine in Tanzania

The expression and metabolic profile of serval hepatic drug metabolizing enzymes is altered by hormonal and physiological changes during pregnancy. Enhanced antimalarial drug metabolism and lower plasma drug exposure may increase the risks of treatment failure, development of resistance and negative birth outcomes. Receiving the same therapy, the pharmacokinetics and treatment outcome of antimalarial drugs may differ between pregnant and non-pregnant women. Knowledge on the pharmacokinetics of antimalarial drugs, and its impact on treatment response in pregnant women is still minimal. In addition, the impact of pharmacogenetic variations on malaria treatment outcome in pregnant women remain to be explored. We are conducting a pharmacogenetic and pharmacokinetic prospective cohort study in pregnant women with uncomplicated Plasmodium falciparum infection treated with artemisinin lumefantrine combination therapy in Tanzania.

This study is funded by grant from Sida.

 

Project 5: Optimization of paediatric antiretroviral therapy in sub Saharan Africa.

Efavirenz (EFV), a potent antiretroviral drug is approved by US-FDA and WHO to treat HIV infected children > 3 years of age. US-FDA has recently expanded the use of efavirenz (EFV) based ART for children aged ≥ 3 months weighing > 3.5 kg. However, waiting for more pharmacokinetic (PK) safety and efficacy data in children, WHO continues to limit the use of EFV in children < 3 years of age.  The current body weight based EFV dose recommendation to treat infant and children is a scaled-down prediction from population PK modelling of data obtained from adults treated with the standard maximum EFV dose (600mg/day). We are conducting a three-phase efavirenz pharmacokinetics, pharmacogenetics and pharmacodynamics based dose optimization study in HIV and HIV-TB co-infected children in Uganda and Ethiopia. Result from this study will provide evidence-based recommendation for policy makers to develop effective pediatric HIV treatment guidelines particularly in Sub-Saharan Africa.

This study is funded by grant from the Swedish research council.

Project 6: Pharmacokinetics and Pharmacogenetics of Cyclophosphamide and tamoxifen for treatment of Breast Cancer patients in Ethiopia.

Breast cancer in women of black African origin is characterized by younger age of onset, clinically aggressive with high prevalence of triple negative tumor, and higher mortality rates than age-matched Caucasian women.  Cyclophosphamide and tamoxifen are the cornerstone of breast cancer chemotherapy. Both drugs are metabolized by genetically polymorphic cytochrome P450 enzymes, and display wide between patient variations in their plasma concentrations. In a cross-sectional study design, we investigate the impact of pharmacogenetics on the pharmacokinetics of cyclophosphamide and tamoxifen, as we as the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced relative dose intensity in Ethiopian breast cancer patients.

This study is funded by grant from Sida.

 

 

 

 

 

 

 

 

 

 

 

Academic honours, awards and prizes

Since 2016 -  Memeber of committee for development research at the Swedish research council.

Since 2014 -   Memeber of the Strategic Advisory Committee for European and Developing Countries Clinical Trial partnership (EDCTP) 

2015- Fellow of the Royal Collage of Physicians of Edinburgh: FRCP (Edin) http://www.rcpe.ac.uk/membership/fellowship

2015 - Fellow of the African Academy of sciences.  

2013 - Honorary Professor of clinical Pharmacology at Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.

Links

Publications

Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations
Bedada W, De Andrés F, Engidawork E, Hussein J, Llerena A, Aklillu E
Scientific reports 2018;8(1):12726-

High Levels of Dual-Class Drug Resistance in HIV-Infected Children Failing First-Line Antiretroviral Therapy in Southern Ethiopia
Tadesse Bt, Kinloch Nn, Baraki B, Lapointe Hr, Cobarrubias Kd, Brockman Ma, et al
Viruses 2018;10(2):-

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians
Aklillu E, Carrillo Ja, Makonnen E, Bertilsson L, Djordjevic N
European journal of clinical pharmacology 2018;74(7):903-911

Neuropsychiatric manifestations among HIV-1 infected African patients receiving efavirenz-based cART with or without tuberculosis treatment containing rifampicin
Mugusi S, Ngaimisi E, Janabi M, Mugusi F, Minzi O, Aris E, et al
European journal of clinical pharmacology 2018;():-

Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
Mutagonda Rf, Kamuhabwa Aar, Minzi Oms, Massawe Sn, Asghar M, Homann Mv, et al
Malaria journal 2017;16(1):267-

Elevated levels of circulating CDH5 and FABP1 in association with human drug-induced liver injury
Mikus M, Drobin K, Gry M, Bachmann J, Lindberg J, Yimer G, et al
Liver international : official journal of the International Association for the Study of the Liver 2017;37(1):132-140

Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs
Petros Z, Lee Mt, Takahashi A, Zhang Y, Yimer G, Habtewold A, et al
Omics : a journal of integrative biology 2017;21(4):207-216

Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back-Looking Forward to Next-Generation Innovation
Petros Z, Makonnen E, Aklillu E
Omics : a journal of integrative biology 2017;21(3):123-131

HLA-B*57 Allele Is Associated with Concomitant Anti-tuberculosis and Antiretroviral Drugs Induced Liver Toxicity in Ethiopians
Petros Z, Kishikawa J, Makonnen E, Yimer G, Habtewold A, Aklillu E
Frontiers in pharmacology 2017;8():90-

Population Pharmacokinetic Model Linking Plasma and Peripheral Blood Mononuclear Cell Concentrations of Efavirenz and Its Metabolite, 8-Hydroxy-Efavirenz, in HIV Patients
Habtewold A, Aklillu E, Makonnen E, Yimer G, Bertilsson L, Burhenne J, et al
Antimicrobial agents and chemotherapy 2017;61(8):-

An Open Letter in Support of Transformative Biotechnology and Social Innovation: SANKO University Innovation Summit in Medicine and Integrative Biology, Gaziantep, Turkey, May 5-7, 2016
Saygılı Eİ, Abou-zeid Ah, Akkın Sm, Aklillu E, Barlas İÖ, Borda-rodriguez A, et al
Omics : a journal of integrative biology 2016;20(4):259-62

Conference Report: First Pharmacogenetics and Precision Medicine Conference in Africa (April 7-9, 2016, Cape Town, South Africa)
Dandara C, Suarez-kurtz G, Aklillu E
Omics : a journal of integrative biology 2016;20(9):496-7

CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients
Maganda Ba, Minzi Om, Ngaimisi E, Kamuhabwa Aa, Aklillu E
The pharmacogenomics journal 2016;16(1):88-95

CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population
Mukonzo Jk, Bisaso Rk, Ogwal-okeng J, Gustafsson Ll, Owen Js, Aklillu E
Pharmacogenomics 2016;17(6):603-13

Genome-wide association and replication study of anti-tuberculosis drugs-induced liver toxicity
Petros Z, Lee Mm, Takahashi A, Zhang Y, Yimer G, Habtewold A, et al
BMC genomics 2016;17(1):755-

High Gastrointestinal Colonization Rate with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Hospitalized Patients: Emergence of Carbapenemase-Producing K. pneumoniae in Ethiopia
Desta K, Woldeamanuel Y, Azazh A, Mohammod H, Desalegn D, Shimelis D, et al
PloS one 2016;11(8):e0161685-

Long-Term Effect of Rifampicin-Based Anti-TB Regimen Coadministration on the Pharmacokinetic Parameters of Efavirenz and 8-Hydroxy-Efavirenz in Ethiopian Patients
Habtewold A, Aklillu E, Makonnen E, Amogne W, Yimer G, Aderaye G, et al
Journal of clinical pharmacology 2016;56(12):1538-1549

Malaria prevalence, severity and treatment outcome in relation to day 7 lumefantrine plasma concentration in pregnant women
Mutagonda Rf, Kamuhabwa Aa, Minzi Om, Massawe Sn, Maganda Ba, Aklillu E
Malaria journal 2016;15(1):278-

Precision Medicine 2.0: The Rise of Glocal Innovation, Superconnectors, and Design Thinking
Dandara C, Endrenyi L, Kolker E, Hekim N, Steuten Lm, Güngör K, et al
Omics : a journal of integrative biology 2016;20(9):493-5

Prevalence and risk factors for efavirenz-based antiretroviral treatment-associated severe vitamin D deficiency: A prospective cohort study
Nylén H, Habtewold A, Makonnen E, Yimer G, Bertilsson L, Burhenne J, et al
Medicine 2016;95(34):e4631-

SLCO1B1 Gene Variations Among Tanzanians, Ethiopians, and Europeans: Relevance for African and Worldwide Precision Medicine
Aklillu E, Habtewold A, Ngaimisi E, Yimer G, Mugusi S, Amogne W, et al
Omics : a journal of integrative biology 2016;20(9):538-45

Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex
Hatta Fh, Lundblad M, Ramsjo M, Kang Jh, Roh Hk, Bertilsson L, et al
Omics : a journal of integrative biology 2015;19(6):346-53

Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial
Amogne W, Aderaye G, Habtewold A, Yimer G, Makonnen E, Worku A, et al
PloS one 2015;10(5):e0122587-

Genesis of EDCTP2
Zumla A, Makanga M, Nyirenda T, Beattie P, Olesen Of, Breugelmans Jg, et al
The Lancet. Infectious diseases 2015;15(1):11-3

Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning From the Pasteur-Bechamp Debates
Host-directed Therapies Network Hd, Zumla A, Maeurer M, Chakaya J, Hoelscher M, Ntoumi F, et al
CLINICAL INFECTIOUS DISEASES 2015;61(9):1432-8

Is there a need to increase the dose of efavirenz during concomitant rifampicin-based antituberculosis therapy in sub-Saharan Africa? The HIV-TB pharmagene study
Habtewold A, Makonnen E, Amogne W, Yimer G, Aderaye G, Bertilsson L, et al
Pharmacogenomics 2015;16(10):1047-64

miRNA-27b levels are associated with CYP3A activity in vitro and in vivo
Ekström L, Skilving I, Ovesjö Ml, Aklillu E, Nylén H, Rane A, et al
Pharmacology research & perspectives 2015;3(6):e00192-

P450 (Cytochrome) Oxidoreductase Gene (POR) Common Variant (POR*28) Significantly Alters CYP2C9 Activity in Swedish, But Not in Korean Healthy Subjects
Hatta Fh, Aklillu E
Omics : a journal of integrative biology 2015;19(12):777-81

The CYP2C19 Intron 2 Branch Point SNP is the Ancestral Polymorphism Contributing to the Poor Metabolizer Phenotype in Livers with CYP2C19*35 and CYP2C19*2 Alleles
Chaudhry As, Prasad B, Shirasaka Y, Fohner A, Finkelstein D, Fan Y, et al
Drug metabolism and disposition: the biological fate of chemicals 2015;43(8):1226-35

The influence of nevirapine and efavirenz-based anti-retroviral therapy on the pharmacokinetics of lumefantrine and anti-malarial dose recommendation in HIV-malaria co-treatment
Maganda Ba, Ngaimisi E, Kamuhabwa Aa, Aklillu E, Minzi Om
Malaria journal 2015;14():179-

The Psychostimulant Khat (Catha edulis) Inhibits CYP2D6 Enzyme Activity in Humans
Bedada W, De Andrés F, Engidawork E, Pohanka A, Beck O, Bertilsson L, et al
Journal of clinical psychopharmacology 2015;35(6):694-9

Towards host-directed therapies for tuberculosis
Host-directed Therapies Network, Zumla A, Maeurer M, Chakaya J, Hoelscher M, Ntoumi F, et al
Nature reviews. Drug discovery 2015;14(8):511-2

CYP2B6 genotype, but not rifampicin-based anti-TB cotreatments, explains variability in long-term efavirenz plasma exposure
Mukonzo Jk, Nanzigu S, Waako P, Ogwal-okeng J, Gustafson Ll, Aklillu E
Pharmacogenomics 2014;15(11):1423-35

Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients
Yimer G, Gry M, Amogne W, Makonnen E, Habtewold A, Petros Z, et al
PloS one 2014;9(4):e94271-

High CYP2A6 enzyme activity as measured by a caffeine test and unique distribution of CYP2A6 variant alleles in Ethiopian population
Aklillu E, Djordjevic N, Carrillo Ja, Makonnen E, Bertilsson L, Ingelman-sundberg M
Omics : a journal of integrative biology 2014;18(7):446-53

Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts
Thulin P, Nordahl G, Gry M, Yimer G, Aklillu E, Makonnen E, et al
LIVER INTERNATIONAL 2014;34(3):367-78

Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes
Mukonzo Jk, Owen Js, Ogwal-okeng J, Kuteesa Rb, Nanzigu S, Sewankambo N, et al
PloS one 2014;9(1):e86919-

Pharmacokinetic and pharmacogenomic modelling of the CYP3A activity marker 4β-hydroxycholesterol during efavirenz treatment and efavirenz/rifampicin co-treatment
Ngaimisi E, Minzi O, Mugusi S, Sasi P, Riedel Kd, Suda A, et al
The Journal of antimicrobial chemotherapy 2014;69(12):3311-9

PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2
Mcdonagh Em, Boukouvala S, Aklillu E, Hein Dw, Altman Rb, Klein Te
Pharmacogenetics and genomics 2014;24(8):409-25

The VKORC1 Asp36Tyr variant and VKORC1 haplotype diversity in Ashkenazi and Ethiopian populations
Sominsky S, Korostishevsky M, Kurnik D, Aklillu E, Cohen Y, Ken-dror G, et al
JOURNAL OF APPLIED GENETICS 2014;55(2):163-71

CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans
Aklillu E, Odenthal-hesse L, Bowdrey J, Habtewold A, Ngaimisi E, Yimer G, et al
BMC INFECTIOUS DISEASES 2013;:536-

Comparisons of CYP2A6 genotype and enzyme activity between Swedes and Koreans
Djordjevic N, Carrillo Ja, Van Den Broek Mp, Kishikawa J, Roh Hk, Bertilsson L, et al
Drug metabolism and pharmacokinetics 2013;28(2):93-7

Copy Number Variation of Fc Gamma Receptor Genes in HIV-Infected and HIV-Tuberculosis Co-Infected Individuals in Sub-Saharan Africa
Machado Lr, Bowdrey J, Ngaimisi E, Habtewold A, Minzi O, Makonnen E, et al
PLOS ONE 2013;8(11):e78165-

Haplotypes in the 5 '-untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism
Gervasini G, Ghotbi R, Aklillu E, Jose Cs, Cabanillas A, Kishikawa J, et al
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2013;54(2):124-32

Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: a parallel-group prospective cohort study in two sub-Saharan Africa populations
Ngaimisi E, Habtewold A, Minzi O, Makonnen E, Mugusi S, Amogne W, et al
PloS one 2013;8(7):e67946-

Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study
Mukonzo Jk, Okwera A, Nakasujja N, Luzze H, Sebuwufu D, Ogwal-okeng J, et al
BMC infectious diseases 2013;13():261-

Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients
Habtewold A, Amogne W, Makonnen E, Yimer G, Nylén H, Riedel Kd, et al
The pharmacogenomics journal 2013;13(6):484-9

beta-defensin Genomic Copy Number Is Associated With HIV Load and Immune Reconstitution in Sub-Saharan Africans
Hardwick Rj, Amogne W, Mugusi S, Yimer G, Ngaimisi E, Habtewold A, et al
JOURNAL OF INFECTIOUS DISEASES 2012;206(7):1012-9

Comparison of N-acetyltransferase-2 enzyme genotype-phenotype and xanthine oxidase enzyme activity between Swedes and Koreans
Djordjevic N, Carrillo Ja, Roh Hk, Karlsson S, Ueda N, Bertilsson L, et al
Journal of clinical pharmacology 2012;52(10):1527-34

High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia: a prospective cohort study
Yimer G, Amogne W, Habtewold A, Makonnen E, Ueda N, Suda A, et al
The pharmacogenomics journal 2012;12(6):499-506

Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz-based HAART with or without tuberculosis co-infection in Tanzania
Mugusi S, Ngaimisi E, Janabi M, Minzi O, Bakari M, Riedel Kd, et al
PloS one 2012;7(7):e40180-

PharmGKB summary: caffeine pathway
Thorn Cf, Aklillu E, Mcdonagh Em, Klein Te, Altman Rb
PHARMACOGENETICS AND GENOMICS 2012;22(5):389-95

PharmGKB summary: very important pharmacogene information for CYP1A2
Thorn Cf, Aklillu E, Klein Te, Altman Rb
PHARMACOGENETICS AND GENOMICS 2012;22(1):73-7

Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania
Mugusi Sf, Ngaimisi E, Janabi My, Mugusi Fm, Minzi Oms, Sasi Pg, et al
ANTIVIRAL THERAPY 2012;17(2):265-74

Search for the molecular basis of ultra-rapid CYP2C9-catalysed metabolism: relationship between SNP IVS8-109A>T and the losartan metabolism phenotype in Swedes
Hatta Fh, Teh Lk, Helldén A, Hellgren Ke, Roh Hk, Salleh Mz, et al
European journal of clinical pharmacology 2012;68(7):1033-42

Effect of Rifampicin and CYP2B6 Genotype on Long-Term Efavirenz Autoinduction and Plasma Exposure in HIV Patients With or Without Tuberculosis
Ngaimisi E, Mugusi S, Minzi O, Sasi P, Riedel Kd, Suda A, et al
CLINICAL PHARMACOLOGY & THERAPEUTICS 2011;90(3):406-13

Frequency of the SLCO1B1 388A > G and the 521T > C polymorphism in Tanzania genotyped by a new LightCycler (R)-based method
Aklillu E, Mugusi S, Ngaimisi E, Hoffmann Mm, Konig S, Ziesenitz V, et al
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2011;67(11):1139-45

HIV/AIDS Patients Display Lower Relative Bioavailability of Efavirenz than Healthy Subjects
Mukonzo Jk, Nanzigu S, Rekic D, Waako P, Roshammar D, Ashton M, et al
CLINICAL PHARMACOKINETICS 2011;50(8):531-40

Long-term effect of efavirenz autoinduction on plasma/peripheral blood mononuclear cell drug exposure and CD4 count is influenced by UGT2B7 and CYP2B6 genotypes among HIV patients
Habtewold A, Amogne W, Makonnen E, Yimer G, Riedel Kd, Ueda N, et al
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2011;66(10):2350-61

N-acetyltransferase-2 (NAT2) Gene Polymorphisms and Enzyme Activity in Serbs: Unprecedented High Prevalence of Rapid Acetylators in a White Population
Djordjevic N, Carrillo Ja, Ueda N, Gervasini G, Fukasawa T, Suda A, et al
JOURNAL OF CLINICAL PHARMACOLOGY 2011;51(7):994-1003

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients
Yimer G, Ueda N, Habtewold A, Amogne W, Suda A, Riedel Kd, et al
PLOS ONE 2011;6(12):e27810-

Sex and CYP3A5 genotype influence total CYP3A activity: high CYP3A activity and a unique distribution of CYP3A5 variant alleles in Ethiopians
Gebeyehu E, Engidawork E, Bijnsdorp A, Aminy A, Diczfalusy U, Aklillu E
PHARMACOGENOMICS JOURNAL 2011;11(2):130-7

Carriers of the UGT1A4 142T > G gene variant are predisposed to reduced olanzapine exposure-an impact similar to male gender or smoking in schizophrenic patients
Ghotbi R, Mannheimer B, Aklillu E, Suda A, Bertilsson L, Eliasson E, et al
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2010;66(5):465-74

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking
Ramsjo M, Aklillu E, Bohman L, Ingelman-sundberg M, Roh Hk, Bertilsson L
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2010;66(9):871-7

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans
Mukonzo Jk, Waako P, Ogwal-okeng J, Gustafsson Ll, Aklillu E
THERAPEUTIC DRUG MONITORING 2010;32(3):346-52

Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2-163C > A polymorphism
Djordjevic N, Ghotbi R, Jankovic S, Aklillu E
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2010;66(7):697-703

In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population
Djordjevic N, Carrillo Ja, Gervasini G, Jankovic S, Aklillu E
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2010;66(6):571-8

Long-Term Efavirenz Autoinduction and Its Effect on Plasma Exposure in HIV Patients
Ngaimisi E, Mugusi S, Minzi Om, Sasi P, Riedel Kd, Suda A, et al
CLINICAL PHARMACOLOGY & THERAPEUTICS 2010;88(5):676-84

Allele-specific expression and gene methylation in the control of CYP1A2 mRNA level in human livers
Ghotbi R, Gomez A, Milani L, Tybring G, Syvanen Ac, Bertilsson L, et al
PHARMACOGENOMICS JOURNAL 2009;9(3):208-17

A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans
Mukonzo Jk, Roshammar D, Waako P, Andersson M, Fukasawa T, Milani L, et al
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 2009;68(5):690-9

Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression
Aklillu E, Karlsson S, Zachrisson Oo, Ozdemir V, Agren H
PHARMACOGENETICS AND GENOMICS 2009;19(4):267-75

CORRELATION OF CYP2A6 ENZYME ACTIVITY WITH GENOTYPE AND CIGARETTE SMOKING IN SERBS
Djordjevic N, Carrillo Ja, Gervasini G, Jankovic S, Aklillu E
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY 2009;:21-22

MAO-A and COMT genotypes as possible regulators of perinatal serotonergic symptoms after in utero exposure to SSRIs
Hilli J, Heikkinen T, Rontu R, Lehtimaki T, Kishida I, Aklillu E, et al
EUROPEAN NEUROPSYCHOPHARMACOLOGY 2009;19(5):363-70

N-ACETYLTRANSFERASE-2 (NAT2) GENE POLYMORPHISMS AND ENZYME ACTIVITY IN SERBS: UNPRECEDENTED HIGH PREVALENCE OF RAPID ACETYLATORS IN A WHITE POPULATION
Djordjevic N, Carrillo Ja, Gervasini G, Jankovic S, Aklillu E
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY 2009;:81-81

STEADY STATE EFAVIRENZ PHARMACOKINETICS PROFILE AMONG HIV PATIENTS IN ETHIOPIA
Eyakem A, Amogne W, Yimer G, Makonnen E, Aderaye G, Bertilsson L, et al
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 2009;:6-6

THE AUTO INDUCTION OF EFAVIRENZ METABOLISM AND THE RESULTING EFFECT ON THE EFAVIRENZ STEADY STATE LEVELS IN TANZANIAN PATIENTS
Ngaimisi E, Mugusi S, Minzi O, Sasi P, Janabi M, Mugusi F, et al
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 2009;:7-7

4 beta-Hydroxycholesterol is a new endogenous CYP3A marker: relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians
Diczfalusy U, Miura J, Roh Hk, Mirghani Ra, Sayi J, Larsson H, et al
PHARMACOGENETICS AND GENOMICS 2008;18(3):201-8

Anti-Tuberculosis Therapy-Induced Hepatotoxicity among Ethiopian HIV-Positive and Negative Patients
Yimer G, Aderaye G, Amogne W, Makonnen E, Aklillu E, Lindquist L, et al
PLOS ONE 2008;3(3):e1809-

Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes
Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2008;64(4):381-5

Mutations in CYP1B1 cause primary congenital glaucoma by reduction of either activity or abundance of the enzyme
Chavarria-soley G, Sticht H, Aklillu E, Ingelman-sundberg M, Pasutto F, Reis A, et al
HUMAN MUTATION 2008;29(9):1147-53

VKORC1 Asp36Tyr warfarin resistance marker is common in Ethiopian individuals
Aklillu E, Leong C, Loebstein R, Halkin H, Gak E
BLOOD 2008;111(7):3903-4

Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans
Ghotbi R, Christensen M, Roh Hk, Ingelman-sundberg M, Aklillu E, Bertilsson L
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2007;63(6):537-46

CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine
Aklillu E, Kalow W, Endrenyi L, Harper P, Miura J, Ozdemir V
PHARMACOGENETICS AND GENOMICS 2007;17(11):989-93

CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir
Josephson F, Allqvist A, Janabi M, Sayi J, Aklillu E, Jande M, et al
CLINICAL PHARMACOLOGY & THERAPEUTICS 2007;81(5):708-12

Monoamine metabolites level in CSF are related to the 5-HTT gene polymorphism in treatment-resistant depression
Kishida I, Aklillu E, Kawanishi C, Bertilsson L, Agren H
EUROPEAN NEUROPSYCHOPHARMACOLOGY 2007;:S328-S328

Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression
Kishida I, Aklillu E, Kawanishi C, Bertilsson L, Agren H
NEUROPSYCHOPHARMACOLOGY 2007;32(10):2143-51

A common novel CTP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants
Sim Sc, Risinger C, Dahl Ml, Aklillu E, Christensen M, Bertilsson L, et al
CLINICAL PHARMACOLOGY & THERAPEUTICS 2006;79(1):103-13

Anti-tubercular drug-induced hepatotoxicity in HIV-positive and negative patients
Yimer G, Aseffa A, Aklillu E, Makonnen E, Amogne W, Bobosha K, et al
TOXICOLOGY LETTERS 2006;:S92-S92

CYP3A4 and 3A5 catalysed alprazolam metabolism in vitro and in vivo
Miura J, Aklillu E, Allqvist A, Gustafsson Ll, Jande M, Mirghani Ra, et al
INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY 2006;21(4):A33-A33

CYP3A5 genotype has significant effect on quinine 3-hydroxylation in Tanzanians, who have lower total CYP3A activity than a Swedish population
Mirghani Ra, Sayi J, Aklillu E, Allqvist A, Jande M, Wennerholm A, et al
PHARMACOGENETICS AND GENOMICS 2006;16(9):637-45

Distribution and concordance of phenotypically and genotypically determined acetylation status on patients taking anti-tuberculosis drugs in Ethiopia
Yimer G, Golka K, Aseffa A, Aklillu E, Makonnen E, Amogne W, et al
TOXICOLOGY LETTERS 2006;:S98-S98

Pharmacogenetics for off-patent antipsychotics: reframing the risk for tardive dyskinesia and access to essential medicines
Ozdemir V, Aklillu E, Mee S, Bertilsson L, Albers Lj, Graham Je, et al
EXPERT OPINION ON PHARMACOTHERAPY 2006;7(2):119-33

Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic phenotype
Jiang Zw, Dragin N, Jorge-nebert Lf, Martin Mv, Guengerich Fp, Aklillu E, et al
PHARMACOGENETICS AND GENOMICS 2006;16(5):359-67

Characterization of common CYP1B1 variants with different capacity for benzo[a] pyrene-7,8-dihydrodiol epoxide formation from benzo[a]pyrene
Aklillu E, Ovrebo S, Botnen Iv, Otter C, Ingelman-sundberg M
CANCER RESEARCH 2005;65(12):5105-11

Monoamine metabolites in CSF are related to serotonin transporter promoter gene polymorphism in treatment-resistant major depression.
Kishida I, Aklillu E, Bertilsson L, Agren H, Kawanishi C
NORDIC JOURNAL OF PSYCHIATRY 2005;59(5):413-413

Genetic polymorphisms of CYP1A2 and xanthine oxidase in ethiopians affecting expression: Characterization of novel CYP1A2 haplotypes
Aklillu E, Carrillo Ja, Mekonen E, Bertilsson L, Ingelman-sundberg M
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 2004;31(11):A220-A220

Genetic polymorphism of CYP1A2 in ethiopians affecting induction and expression: Characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1
Aklillu E, Carrillo Ja, Makonnen E, Hellman K, Pitarque M, Bertilsson L, et al
MOLECULAR PHARMACOLOGY 2003;64(3):659-69

Xanthine oxidase activity is influenced by environmental factors in Ethiopians
Aklillu E, Carrillo Ja, Makonnen E, Bertilsson L, Ingelman-sundberg M
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2003;59(7):533-6

Analysis of CYP2C9*5 in Caucasian, Oriental and black-African populations
Yasar U, Aklillu E, Canaparo R, Sandberg M, Sayi J, Roh Hk, et al
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 2002;58(8):555-8

Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in Sweden
Aklillu E, Herrlin K, Gustafsson Ll, Bertilsson L, Ingelman-sundberg M
PHARMACOGENETICS 2002;12(5):375-83

Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethiopian population
Aklillu E, Oscarson M, Hidestrand M, Leidvik B, Otter C, Ingelman-sundberg M
MOLECULAR PHARMACOLOGY 2002;61(3):586-94

Genetic polymorphism of cytochrome P4502C9 in a Caucasian and a black African population
Scordo Mg, Aklillu E, Yasar U, Dahl Ml, Spina E, Ingelman-sundberg M
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 2001;52(4):447-50

Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles
Aklillu E, Persson I, Bertilsson L, Johansson I, Rodrigues F, Ingelmansundberg M
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1996;278(1):441-6

S-mephenytoin hydroxylation phenotype and CYP2C19 genotype among ethiopians
Persson I, Aklillu E, Rodrigues F, Bertilsson L, Ingelmansundberg M
PHARMACOGENETICS 1996;6(6):521-6

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