Rifampicin and Ketoconazole Modulation of Intestinal Transport of Carbamazepine in Rats

DOI:

https://doi.org/10.37285/ijpsn.2013.6.4.12

Authors

  • Y.M Rao
  • Adukondalu Devandla
  • Shravan Kumar Yamsani

Abstract

Many drug substances interact with each other and affect the CYP enzyme system and transport properties of other drugs.  The present study was aimed to investigate the effect of ketoconazole and rifampicin pre-treatment on the transport of carbamazepine across the intestine in rats. The transport of carbamazepine across different parts of intestine was studied by the everted and non-everted sac methods. The control and ketoconazole (80 mg/kg) and rifampicin (60 mg/kg) pre-treated rats were sacrificed and the intestine was harvested. The sacs of intestine were   prepared, treated with carbamazepine solution and then placed in Dulbecco’s buffer. Samples were collected periodically and the drug content was estimated using HPLC method. The results show that there was a significant (p<0.05) difference in the transport of carbamazepine from the intestinal sacs of pretreated with ketoconazole and rifampicin as compared to control. It appears that ketoconazole and rifampicin may affect the intestinal transport of carbamazepine and hence may result in pharmacokinetic interactions.  

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Everted sac, Non-everted sac, Induction, Inhibition, CYP3A4

Downloads

Published

2013-12-31

How to Cite

1.
Rao Y, Devandla A, Yamsani SK. Rifampicin and Ketoconazole Modulation of Intestinal Transport of Carbamazepine in Rats. Scopus Indexed [Internet]. 2013 Dec. 31 [cited 2024 Nov. 19];6(4):2294-8. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/692

Issue

Section

Research Articles

References

Ballent M, Lifschitz A, Virkel G, Sallovitz J and Lanusse C (2006). Modulation of the p-glycoprotein-mediated intestinal secretion of ivermectin: in vitro and in vivo assessments. Drug Metab Dispos 34: 457-463.

Boyce MJ, Baisley KJ and Warrington SJ (2012). Pharmacokinetic interaction between domperidone and ketoconazole leads to QT prolongation in healthy volunteers: a randomized, placebo-controlled, double-blind, crossover study. Bri J Clin Pharmacol 73(3): 411–421.

Douglas CR (1985). Atlas of Drug Reactions. New York, NY: ChurchillLivingstone 123.

Frank GJ and Tukey RH (2006). Drug Metabolism. In Laurence Brunton, John Lazo, Keith Parker (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill, pp-79.

Giessmann T, Warzok R and Cascorbi I (2004). Carabamazepine regulates intestinal p-glycoprotein and multi drug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther 76:192-197.

Kaul S and Ritschel WA (1981). Studies of the intestinal transfer of coumarin and 7- hydroxycoumarin across guinea pig and rat small intestine. Arzneim Forsch 31: 790-795.

Kolars JC, Schmiedlin-Ren P, Schuetz JD, Fang C and Watkins PB (1992). Identification of rifampin- inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 90: 1871-1878.

Kyoung SL, Jung HP, Hwa JL and Sandy R (2012). Preclinical study of a potent P-glycoprotein and cytochrome P450 enzyme inducer rifampicin changing pharmacokinetic parameters of risperidone and its metabolite, 9-hydroxyrisperidone, using a rat model. J Pharma Invest 42: 345–351.

Mahatthanatrakul W, Sriwiriyajan S, Ridtitid W, Boonleang J, Wongnawa M, Rujimamahasan N and Pipatrattanaseree W (2012). Effect of cytochrome P450 3A4 inhibitor ketoconazole on risperidone pharmacokinetics in healthy volunteers. J Clin Pharm Ther 37(2): 221-225.

Ruan LP, Chen S, Yu BY, Zhu DN and Cordell GA Qiu SX (2006). Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem 41: 605-610.

Sebastian H, Michael KB, Ashish S, Gerhard N, Ute L, Wolfgang T and Paul A R (2012) Decrease in the oral bioavailability of dabigatran etexilate after co-medication with rifampicin. Bri J Clin Pharmacol 74(3): 490–500.

Susan MB, Anthony JT and Katzung BG. (2005). Katzung & Trevor's Pharmacology. New York, Lange Medical Books/McGraw Hill, Medical Pub Division 10Th Ed. 34.

Taher M, Saghaie L and Abrahilmi M (2004). Investigation of Intestinal Absorption of Pyridinones in Rat. Iranian J Pharm Res 3: 201-207.

Yumoto R, Murakami T, Yuko N, Risa H, Junya and Mikihisa T (1998). Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A related compounds. J Exp Ther 289: 149-152.