Pharmacokinetic interaction between rifampin and zidovudine

Burger, David M.; Meenhorst, Pieter L.; Koks, C. H. W.; Beijnen, Jos H.

doi:10.1128/aac.37.7.1426

Cited by 71 publications

(31 citation statements)

References 27 publications

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“…clearance of zidovudine when rifampin was coadministered, possibly as a result of the induction of enzymes by rifampin, and the zidovudine plasma concentration increased 2-fold with the discontinuation of rifampin (29). Similarly, rifabutin caused a 32% reduction in the area under the concentration-time curve (AUC) and zidovudine clearance increased by 43% in zidovudine-rifabutin combination therapy (30).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family

Parvez

Kaisar

Shin

et al. 2016

Antimicrob Agents Chemother

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b Twenty-two currently marketed antituberculosis drugs were comprehensively evaluated for their inhibitory effect on organic anionic transporter (OAT)-and organic cation transporter (OCT)-mediated uptake using stably transfected HEK293 cells in vitro. We observed moderate to strong inhibitory effects on OAT1-and OAT3-mediated para-aminohippurate (PAH) uptake and OCT1-and OCT2-mediated N-methyl-4-phenylpylidinium acetate (MPP ؉ ) uptake. Ciprofloxacin, linezolid, para-aminosalicylic acid (PAS), and rifampin were observed to have strong inhibitory effects, with the concentrations for a 50% inhibitory effect (IC 50 s) being 35.1, 31.1, 37.6, and 48.1 M, respectively, for OAT1 and >100, 21.9, 24.6, and 30.2 M, respectively, for OAT3. Similarly, pyrazinamide, rifabutin, and levofloxacin were observed to have inhibitory effects, with IC 50 values being 36.5, 42.7, and 30.3 M, respectively, for OCT1 and with the IC 50 value for PAS being 94.2 M for OCT2. In addition, we used zidovudine and metformin as clinically prescribed substrates of OATs and OCTs, respectively, and zidovudine and metformin uptake was also strongly inhibited by the antituberculosis drugs. Among the tested drugs, the highest drug-drug interaction (DDI) indexes were found for PAS, which were 9.3 to 13.9 for OAT1 and 12.0 to 17.7 for OAT3, and linezolid, which were 1.18 to 2.15 for OAT1 and 1.7 to 3.01 for OAT3. Similarly, the DDI indexes of pyrazinamide and levofloxacin were 0.57 and 0.30, respectively, for OCT1, and the DDI index of PAS was 3.8 for OCT2, suggesting a stronger possibility (DDI index value cutoff, >0.1) of in vivo DDIs. This is the first comprehensive report of the inhibitory potential of anti-TB drugs on OAT-and OCT-mediated uptake of prototype and clinically prescribed substrate drugs in vitro, providing an ability to predict DDIs between anti-TB drugs and other coprescribed drugs in clinical studies in vivo. So far, 400 human solute carrier family (SLC) transporter proteins have been identified as a superfamily and have been classified into 52 different subfamilies (1). The organic cation transporter (OCT; SLC22 subfamily) and organic anion transporter (OAT; SLC22 subfamily) families play a major role in the disposition and pharmacology of drug substances (2). Among these, organic cation transporter OCT1 (SLC22A1) appears to be highly expressed in the liver of all species and in many tissues, although intriguing differences between species have been noted. OCT1 expression is restricted to the basolateral membrane of proximal tubular cells, with the greatest expression being apparent in an early segment (segment S1) of superficial, midcortical, and juxtamedullary nephrons (3), whereas OCT2 (SLC22A2) is expressed in the kidney and appears to be restricted to the basolateral membrane of proximal tubular cells (4).The function of OCTs includes mediation of the transport of organic cations into or out of cells. Not all but many organic cations (of endogenous and exogenous origin) are substrates of OCTs. Endogenous organic cations includ...

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Section: Discussionmentioning

confidence: 99%

Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family

Parvez

Kaisar

Shin

et al. 2016

Antimicrob Agents Chemother

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“…Rifampin is a common interacting drug involved in glucuronidation-mediated DDI (13)(14)(15)(16)(17)(18). In our study, the C max and AUC of morinidazole in healthy subjects were decreased significantly, by around 20% to 30%, after pretreatment with rifampin, while only the C max of M8-1was increased 1.3-fold, without a change of AUC.…”

Section: Discussionmentioning

confidence: 99%

Effects of Rifampin and Ketoconazole on Pharmacokinetics of Morinidazole in Healthy Chinese Subjects

Pang

Zhang

Gao

et al. 2014

Antimicrob Agents Chemother

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Morinidazole, a 5-nitroimidazole antimicrobial drug, has been approved for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections in China. It was reported that drug-drug interaction happened after the coadministration of ornidazole, an analog of morinidazole, and rifampin or ketoconazole. Therefore, we measured the plasma pharmacokinetics (PK) of morinidazole and its metabolites in the healthy Chinese volunteers prior to and following the administration of rifampin or ketoconazole using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the concentration-time curve from time 0 to time t (AUC 0-t ) and maximum concentration in serum (C max ) of morinidazole were decreased by 28% and 23%, respectively, after 6 days of exposure to 600 mg of rifampin once daily; the C max s of N ؉ -glucuronides were increased by 14%, while their AUC 0-t s were hardly changed. After 7 days of exposure to 200 mg of ketoconazole once daily, the AUC 0-t and C max of the parent drug were not affected significantly. C max s of N ؉ -glucuronides were decreased by 23%; AUC 0-t s were decreased by 14%. The exposure of sulfate conjugate was hardly changed after the coadministration of rifampin or ketoconazole. Using recombinant enzyme of UGT1A9 and human hepatocytes, the mechanism of the altered PK behaviors of morinidazole and its metabolites was investigated. In human hepatocytes, ketoconazole dose dependently inhibited the formation of N ؉ -glucuronides (50% inhibitory concentration [IC 50 ], 1.5 M), while rifampin induced the mRNA level of UGT1A9 by 28% and the activity of UGT1A9 by 53%. In conclusion, the effects of rifampin and ketoconazole on the plasma exposures of morinidazole and N ؉ -glucuronide are less than 50%; therefore, rifampin and ketoconazole have little clinical significance in the pharmacokinetics of morinidazole. Morinidazole is developed as a 5-nitroimidazole antimicrobial injection with potent activities against anaerobic Gram-negative sporeless bacilli and Gram-positive cocci (1). Its efficacy against Clostridium perfringens, Bacteroides fragilis, Veillonella parvula, Bacteroides distasonis, Bacteroides ovatus, Bacteroides vulgatus, and Bacteroides melaninogenicus is equal to that of ornidazole and superior to those of metronidazole and tinidazole. It has been approved for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections in China. However, its antibacterial spectrum is still limited; thus, there is the possibility of concomitant administration with other antibacterial agents in the treatment of mixed infections. It was reported that drug-drug interaction (DDI) happened after the coadministration of ornidazole, an analog of morinidazole, with rifampin or ketoconazole. The pharmacokinetic parameters of ornidazole in healthy volunteers-area under the curve (AUC), peak concentration (C max ), elimination half-life (t 1/2 ), and clearance (CL)-were decreased by 21.16%, 20.43%, 18.11%, and 32.14%, respectively, by rifampin. The altered pharmacok...

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“…It is probably less well known that this drug also induces phase II metabolism. More specifically, rifampicin induces uridine diphoshate glucuronosyltransferase and sulphotransferase, thereby reducing plasma concentrations of rofecoxib, mycophenolate mofetil, lamotrigine, zidovudine, and propafenone [13,[28][29][30][31][32][33][34]. A similar mechanism may be involved in the interaction with moxifloxacin, because this drug undergoes phase II biotransformation and will be excreted as a sulpho-compound or as glucuronide via the kidneys (2.5% and 14%, respectively) and the feces (34% and 14%, respectively) [35].…”

Section: Discussionmentioning

confidence: 99%

Rifampicin Reduces Plasma Concentrations of Moxifloxacin in Patients with Tuberculosis

Nijland

Ruslami

Suroto³

et al. 2007

Clinical Infectious Diseases

152

120

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Background. The long duration of the current tuberculosis (TB) treatment is demanding and warrants the development of new drugs. Moxifloxacin shows promising results and may be combined with rifampicin to shorten the duration of TB treatment. Rifampicin induces the phase II metabolic enzymes that are involved in the biotransformation of moxifloxacin. Therefore, the interaction between rifampicin and moxifloxacin should be investigated.Patients and methods. Nineteen Indonesian patients with pulmonary TB who were in the last month of their TB treatment completed a 1-arm, 2-period, fixed-order pharmacokinetic study. In phase 1 of the study, they received 400 mg of moxifloxacin every day for 5 days in addition to 450 mg of rifampicin and 600 mg of isoniazid 3 times per week. In phase 2 of the study, after a 1-month washout period, patients received moxifloxacin for another 5 days (without rifampicin and isoniazid). A 24-h pharmacokinetic curve for moxifloxacin was recorded on the last day of both study periods, and its pharmacokinetic parameters were evaluated for an interaction with rifampicin, using a bioequivalence approach.Results. Coadministration of moxifloxacin with rifampicin and isoniazid resulted in an almost uniform decrease in moxifloxacin exposure (in 18 of 19 patients). The geometric means for the ratio of phase 1 area under the curve to phase 2 area under the curve and for the ratio of phase 1 peak plasma concentration to phase 2 peak plasma concentration were 0.69 (90% confidence interval, 0.65-0.74) and 0.68 (90% confidence interval, 0.64-0.73), respectively. The median time to reach peak plasma concentration for moxifloxacin was prolonged from 1 h to 2.5 h when combined with rifampicin and isoniazid ( ). P p .003 Conclusions. Coadministration of moxifloxacin with intermittently administered rifampicin and isoniazid results in reduced moxifloxacin plasma concentrations, which is most likely the result of induced glucuronidation or sulphation by rifampicin. Further studies are warranted to evaluate the impact of the interaction on the outcome of TB treatment.

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Pharmacokinetic interaction between rifampin and zidovudine

Cited by 71 publications

References 27 publications

Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family

Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family

Effects of Rifampin and Ketoconazole on Pharmacokinetics of Morinidazole in Healthy Chinese Subjects

Rifampicin Reduces Plasma Concentrations of Moxifloxacin in Patients with Tuberculosis

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