title: Effect of carbamazepine on the pharmacokinetic parameters of CDRI-97/78 following coadministration to rats.
abstract: Coadministration of 2 or more drugs may result in unexpected toxicity. This study aimed to evaluate the effect of carbamazepine coadministration on the pharmacokinetics of CDRI-97/78, an 1,2,4-trioxane antimalarial agent. Firstly, 97/78 was administered alone and then 97/78 and carbamazepine were coadministered to male and female rats. An revalidated LC-MS/MS method was used for quantitation of 97/63 since 97/78 is instantly and completely converted to 97/63 (an in-vivo active metabolite). The Tmax and Cmax values of 97/63 were 1.75±0.77 h and 862±306 ng/mL in male rats whereas in female rats they were 5.45±0.76 h and 662.75±95.09 ng/mL after a single dose of 97/78 alone. However, following coadministration of 97/78 and carbamazepine, the values for Tmax and Cmax were 1.06±0.16 h and 533±153 ng/mL in male rats and 2.23±1.93 h and 636.5±112.4 ng/mL in female rats. The half life of 97/63 following a single oral dose of 97/78 or coadministration with carbamazepine to male rats was 6.98±0.63 h and 6.64±0.54 h, respectively; the values in female rats were 7.5±0.5 h and 5.48±0.37 h. A statistically insignificant difference (P>0.05) was observed with the student t-test for the pharmacokinetic parameters of 97/63 following oral administration of 97/78 alone or coadministration of 97/78 and carbamazepine except for MRT in female rats. Intersex statistical comparison also showed an insignificant difference for 97/63 following oral administration of 97/78 alone or in combination with carbamazepine except for MRT, which supports coadministration of 97/78 and carbamazepine.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Kushwaha
authors.forename: A
authors.initials: A
authors.lastname: Misra
authors.forename: N
authors.initials: N
authors.lastname: Gautam
authors.forename: Y
authors.initials: Y
authors.lastname: Singh
authors.forename: H
authors.initials: H
authors.lastname: Kumar
authors.forename: H H
authors.initials: HH
authors.lastname: Siddiqui
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D002853:Chromatography, Liquid; D004347:Drug Interactions; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D000927:Anticonvulsants; D019086:Bridged Bicyclo Compounds, Heterocyclic; C574493:CDRI-97-78; D002220:Carbamazepine