Drug Res (Stuttg) 2013; 63(06): 282-288
DOI: 10.1055/s-0033-1334921
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Carbamazepine on the Pharmacokinetic Parameters of CDRI-97/78 Following Coadministration to Rats

H. N. Kushwaha
1   Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India
A. Misra
1   Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India
N. Gautam
1   Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India
Y. Singh
1   Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India
H. Kumar
1   Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India
H. H. Siddiqui
2   Faculty of Pharmacy, Integral University, Kursi Road, Lucknow, India
S. K. Singh
1   Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India
› Author Affiliations
Further Information

Publication History

received 14 July 2012

accepted 07 January 2013

Publication Date:
04 April 2013 (online)


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.

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