Effects of artemisinin, artemether, arteether on the pharmacokinetics of carbamazepine.
The effect of artemisinin, artemether and arteether on the pharmacokinetics of carbamazepine in rabbits was studied. In a cross-over study, carbamazepine 40 mg/kg/day orally was given daily for 7 days. On day 7, blood samples were taken at various time intervals between 0 and 24 h. In the artemisinin group, carbamazepine was administered for 7 days as above. On day 8, artemisinin 82 mg/kg followed by 41 mg/kg on the 9th and 10th day along with carbamazepine 40 mg/kg/day was administered and blood samples drawn as above. Artemether 10 mg/kg i.m. was given on day 8 followed by 5 mg/kg i.m. for 2 days. Arteether 10 mg/kg i.m. was given from day 8 for 3 days. Plasma carbamazepine levels were assayed by high-performance liquid chromatography and pharmacokinetic parameters calculated. In all the groups there was an increase in the AUC(0-infinity) when carbamazepine was co-administered with artemisinin, artemether or arteether. The increase in AUC(0-infinity) (22.78 +/- 4.71 to 63.10 +/- 12.29), Cmax (2.76 +/- 0.77 to 7.02 +/- 1.08), Tmax (2.83 +/- 0.17 to 4.16 +/- 0.40) was statistically significant when artemether was given along with carbamazepine (p < 0.05). In the other groups the increase was not significant. These results suggest artemisinin compounds alter the pharmacokinetics of carbamazepine with significant change in the bioavailability. Confirmation of these results in human studies will warrant changes in carbamazepine dose or frequency when either of these antimalarials is co-administered with it.
Sukhija
Manpreet
M
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Medhi
Bikash
B
Pandhi
P
P
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics; D000962:Antimalarials / Q000494:pharmacology*; D019540:Area Under Curve; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology; D001682:Biological Availability; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006207:Half-Life; D007273:Injections, Intramuscular; D007783:Lactones / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D012717:Sesquiterpenes / Q000494:pharmacology; D013535:Suspensions
D000927:Anticonvulsants; D000962:Antimalarials; D037621:Artemisinins; D065607:Cytochrome P-450 Enzyme Inhibitors; D007783:Lactones; D012717:Sesquiterpenes; D013535:Suspensions; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System; D000077549:Artemether; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C055141:artemotil; C075875:artemisin