Pharmacokinetic Drug Interactions with Rifampicin

Venkatesan, K

doi:10.2165/00003088-199222010-00005

Cited by 124 publications

(72 citation statements)

References 110 publications

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“…Induction of CYP results in increased elimination of co-administered drugs, whose metabolism is mediated by the same isozymes, and this is often related to the insufficient pharmacological effects. There have been some reports showing such unexpected interactions by RF with clinically important drugs including cyclosporine, nifedipine, oral contraceptives, phenytoin, and theophylline (4,5).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Antituberculosis Drugs on Human Cytochrome P450-Mediated Activities

et al. 2004

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Abstract. The potential for drug-drug interactions mediated by the inhibition of cytochrome P-450 (CYP) were concerned during antituberculosis therapy. However, the information regarding human CYP inhibition by antituberculosis drugs is limited to isoniazid. In the current study, we examined the inhibitory effects of pyrazinamide and ethionamide, both of which are chemically related to isoniazid, on the CYP-mediated activities in human liver microsomes and compared them to that of isoniazid. No remarkable effects on any CYP activities were observed by pyrazinamide and ethionamide. In contrast, in addition to the reported inhibitory effect of isoniazid on CYP1A2, CYP2A6, CYP2C19, and CYP3A activities, our results newly showed its effect on CYP2C9 and CYP2E1 activities. Isoniazid showed potent direct inhibitory effect on S-warfarin 7-hydroxylation, while a preincubation step in the presence of NADPH was needed to inhibit chlorzoxazone 6-hydroxylation. Furthermore, irreversible inhibition of CYP2C19 activity by isoniazid was also observed in the dilution study. These results suggested that pyrazinamide and ethionamide did not seem to cause drug interactions mediated by the inhibition of CYP. In contrast, isoniazid might contribute to the severe drug interactions by a different inhibitory mechanism depending on each of the CYP isozymes, in addition to the reported observations.

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Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Antituberculosis Drugs on Human Cytochrome P450-Mediated Activities

et al. 2004

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“…3) In addition, rifampicin and its analogue rifabutin increase their own metabolism after repeated administration to patients. 4) Rifampicin also causes an increase in the urinary ratio of 6b hydroxycortisol to 17 hydroxycorticosterone, indicating the induction of CYP3A4 in vivo.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Gene Induction of Drug-Metabolizing Enzymes and Transporters in Primary Culture of Human Hepatocytes Using High-Sensitivity Real-Time Reverse Transcription PCR

et al. 2002

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In the present study, the induction of drug-metabolizing enzymes and transporters was evaluated by analyzing mRNA expression in human hepatocytes after exposure to various compounds. The compounds tested included typical enzyme inducers, rifampicin and omeprazole, and controls. All experiments were performed in the presence of 0.1％ DMSO. Analysis was performed by the real-time reverse-transcription polymerase chain reaction method (RT PCR) in the presence of TaqMan probes using an ABI PRISM 7700 Sequence Detector system. A new analytic method to quantify mRNA levels in small numbers of human hepatocytes has been developed for phase I enzymes, phase II enzymes, and transporters. The levels of CYP1A1, CYP2B6, CYP2C8, CYP3A4, CYP3A5, ADH3, and ABCG1 mRNA in human hepatocytes increased after exposure to rifampicin. The levels of CYP1A1, CYP2B6, CYP3A4, CYP3A5, and ABCG1 mRNA recovered after a change to media without rifampicin. The levels of CYP1A1, CYP1A2, CYP1B1, ALDH3, and ALDH6 mRNA increased after exposure to omeprazole, and recovered after a change to media without omeprazole. On the other hand, the levels of ADH3 and ABCB4 mRNA decreased after exposure to omeprazole, and recovered after a change to media without omeprazole. In conclusion, these results demonstrate the applicability of quantitative real-time RT PCR to the evaluation of the gene induction and recovery of drug-metabolizing enzymes and transporters after exposure to drugs in human hepatocytes.

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“…Quinine is widely used to treat malaria in endemic phylline, antipyrine, hexobarbitone and cyclosporine malaria areas where Plasmodium falciparum is resist- [2][3][4][5][6][7][8]. It has been shown that rifampicin decreases the ant to chloroquine.…”

Section: Introductionmentioning

confidence: 99%

“…drug metabolism in humans [1,2] and is known to Isoniazid, another anti-tuberculosis drug, inhibits interact with a number of drugs such as warfarin, hepatic oxidative metabolism of a number of drugs digitoxin, dapsone, chlorpropamide, metoprolol, theosuch as phenytoin (metabolised by CYP2C9), carba- [3,[14][15][16]. This suggests that inhibition of oxidative drug metabolism by isoniazid is not selective [17].…”

Section: Introductionmentioning

confidence: 99%

Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man.

Wanwimolruk

Kang

Coville

et al. 1995

Brit J Clinical Pharma

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The effect of rifampicin and isoniazid pretreatment on the pharmacokinetics of quinine after a single oral dose (600 mg quinine sulphate) was studied in nine healthy young Thai male volunteers using a three-way randomized crossover design. Subjects were studied over three 2 day periods, during which they received no pretreatment, or pretreatment with daily 600 mg p.o. rifampicin for 2 weeks, or isoniazid 300 mg p.o. daily for 1 week, prior to quinine administration. The mean (+ s.d.) clearance (CL/F) of quinine coadministered with rifampicin (0.87 ± 0.35 1 h-1 kg-') was significantly greater than that of quinine alone (0.14 ± 0.05 1 h-1 kg-'). The mean difference in clearance from the control treatment was 0.73 1 h-1 kg-', with 95% confidence interval (C.I.) of 0.48 to 0.98. The unbound clearance (CLu/F) of quinine, which reflects the activity of the drug-metabolizing enzymes, was considerably greater (6.9-fold) in subjects when rifampicin was coadministered with quinine than that of quinine alone (6.9 ± 3.6 vs 1.0 ± 0.5 1 h-1 kg-'; the 95% C.I. for the mean difference was 3.3 to 8.5). The mean elimination half-life of quinine when coadministered with rifampicin (5.5 ± 3.0 h) was significantly shorter than when quinine was given alone (11.1 ± 3.0 h; the 95% C.I. for the mean difference was -8.6 to -2.6). In contrast to rifampicin, pretreatment for 1 week with 300 mg oral isoniazid had no significant effects on the pharmacokinetics of quinine. These results indicate that rifampicin pretreatment caused a marked increase (6.2-fold) in the clearance of quinine, possibly due to enzyme induction. The extent to which the elimination of quinine is enhanced by the concomitant administration of rifampicin is likely to have important clinical consequences. Although the clinical significance of these findings is unknown, they indicate the need for caution in the administration of quinine to patients who are concurrently taking rifampicin as an anti-tuberculosis medication.

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Pharmacokinetic Drug Interactions with Rifampicin

Cited by 124 publications

References 110 publications

Inhibitory Effect of Antituberculosis Drugs on Human Cytochrome P450-Mediated Activities

Inhibitory Effect of Antituberculosis Drugs on Human Cytochrome P450-Mediated Activities

Evaluation of Gene Induction of Drug-Metabolizing Enzymes and Transporters in Primary Culture of Human Hepatocytes Using High-Sensitivity Real-Time Reverse Transcription PCR

Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man.

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