Urban Hellgren group
The main overall aim is to improve the treatment of malaria. We focus on the pharmacokinetics and pharmacodynamics of antimalarial drugs.
Drug concentrations in small amounts of capillary blood dried on filter papers are analyzed by sensitive and specific HPLC or LC-MS methods. This allows for repeated sampling also in children. Population pharmacokinetic methods are applied to elucidate the importance of different demographic (age, weight etc) and other variables for drug disposition.
Keywords: Antimalarial drugs, pharmacokinetics, pharmacodynamics
|Urban Hellgren, Group Leader, MD, Associate professor Head tropical and travel medicine, Department of Infectious Diseases, Karolinska University Hospital Huddinge and Unit for Infectious Diseases and Dermatology, Department of Medicine Huddinge, Karolinska Institutet.|
|Norah Mwebaza, MD, PhD student Department of Pharmacology and Therapeutics, Makerere University, Kampala, Uganda|
- Celstino Obua, MD, Associate professor
- Deputy Principal, College of Health Sciences, Makerere University, Kampala, Uganda
- Lars L. Gustafsson, MD, Professor
- Department of Clinical Pharmacology, Karolinska University Hospital Huddinge
- Markus Jerling, MD PhD
- Markus Jerling Consulting AB
Co-formulated Artemether-Lumefantrine [AL, Coartem®] is currently the first-line treatment for uncomplicated falciparum malaria in Uganda.
Artemether is rapidly absorbed and metabolized to the active but rapidly eliminated dihydroartemisinin. Lumefantrine (L) is the long acting partner drug (t1/2 = 4.5 -10 days), critical for cure of malaria since it is responsible for eliminating residual malaria parasites left after 3 days of short acting artemether (A) exposure. The bioavailability of L is highly food-dependent. It is increased 16-fold when given with a high fat meal and it is recommended to take the drug with milk to increase uptake. Detailed pharmacokinetics studies of AL have not been done in African children and the recommended dosage schedule is not based on pharmacokinetic data.
To establish the effect of local food intake on the bioavailability of lumefantrine in healthy adult volunteers and the population pharmacokinetics in under five year old children with uncomplicated falciparum malaria in order to develop rational dosage recommendations.
To explore the effects of selected local food on the bioavailability of lumefantrine among healthy Ugandan adults after a single oral dose of co-formulated AL.
To develop a liquid chromatography plus mass spectrometry (LC + MS) method for determination L and active metabilite with a high sensitivity that will allow determinations of concentrations in capillary blood up to four weeks after drug intake.
To describe the population pharmacokinetics of L among under five year old children in Uganda.
Treated with AL for uncomplicated falciparum malaria.
The studies are supported by grants from SIDA.