Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria.
The pharmacokinetics of increasing doses of an intrarectal Cinchona alkaloid combination containing 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine (Quinimax) was compared to that of parenteral regimens in 60 children with moderate malaria. Quinine exhibited a nonlinear pharmacokinetics, suggesting a saturation of rectal resorption. When early rejections appeared, blood quinine concentrations decreased by 30 to 50% and were restored by an immediate half-dose administration of the drug. Rectal administration of doses of 16 or 20 mg/kg of body weight led to concentration-time profiles in blood similar to those of parenteral regimens and could be an early treatment of childhood malaria.
Pussard
Eric
E
Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France. eric.pussard@bct.ap-hop-paris.fr
Straczek
Celine
C
Kaboré
Idrissa
I
Bicaba
Auguste
A
Balima-Koussoube
Tatiana
T
Bouree
Patrice
P
Barennes
Hubert
H
D000285:Administration, Rectal; D000293:Adolescent; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D002930:Cinchona Alkaloids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D007408:Intestinal Absorption; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000962:Antimalarials; D002930:Cinchona Alkaloids; D011803:Quinine