Existence of antimalarial formulations with low bioavailability in Tanzania.
The main objective of this work was to assess the relative bioavailability of two tablet formulations containing sulfadoxine/pyrimethamine (SP) and marketed in Tanzania. Twelve healthy volunteers were randomized to receive a single oral dose of three SP tablets each containing 500 mg sulfadoxine (SDX) and 25 mg pyrimethamine (PYR) in a form of either A (a locally manufactured SP tablet formulation, manufactured by a local pharmaceutical industry in Tanzania) or B (Fansidar), Hoffmann La Roche, Basel, Switzerland, an innovator's SP) after an overnight fasting. Serial blood samples (100 microL) were collected from a finger prick in duplicate up to 10 days and dried on Whatman filter paper. The samples were assayed for SDX and PYR using high-performance liquid chromatographic methods. Pharmacokinetic parameters of SDX and PYR were estimated by single compartment method. The pharmacokinetics of formulation A--maximum plasma concentration, the areas under the plasma concentration--time curve and the relative bioavailability (A versus B) were significantly lower than those of formulation B (P < 0.1). These observed differences indicate bioinequivalence between the two products.
Minzi
Omary M S
OM
Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University College of Health Sciences, Dar es Salaam. ominzi@muchs.ac.tz
Massele
Amosy
A
Justin-Temu
Mary
M
Ericsson
Orjan
O
Gustafsson
Lars L
LL
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011739:Pyrimethamine / Q000493:pharmacokinetics*; D011786:Quality Control; D016037:Single-Blind Method; D013413:Sulfadoxine / Q000493:pharmacokinetics*; D013636:Tanzania; D013810:Therapeutic Equivalency
D000962:Antimalarials; D004338:Drug Combinations; D016568:Drugs, Generic; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine