Pharmacokinetics of pyrimethamine in healthy young volunteers using a new solid phase extraction/HPLC method.
The single dose pharmacokinetics of pyrimethamine were determined in 12 healthy young volunteers using a newly developed fully automated analytical system which combines liquid solid extraction on disposable extraction columns and high performance liquid chromatography. This technique is highly sensitive (detection 1 ng/ml) and reproducible. Following a 50mg dose of the drug, the plasma concentration peaked at 0.48 0.13 g/ml (msd) and was attained 2.5 hours (median value) post dosing. Thereafter, the plasma level of pyrimethamine decreased slowly, the level at 336 hours after administration being still about 40 ng/ml. The area under the plasma concentration-time curve (AUC0-inf) was 56.8 18.4 h.mg/ml. The volume of distribution Vd was: 2.42 1.25 l/kg and the total clearance: 15.55 4.48 ml/h/kg. Urinary excretion represented about 20% to 40% of the dose after seven days of the administered dose.
Le Liboux
A
A
Rhône Poulenc Santé, Antony, France.
Duquesne
H
H
Montay
G
G
Chassard
D
D
Pichard
E
E
Thebault
J J
JJ
Frydman
A
A
Gaillot
J
J
D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D011739:Pyrimethamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets
D007202:Indicators and Reagents; D013607:Tablets; D011739:Pyrimethamine