Effects of a concomitant single oral dose of rifampicin on the pharmacokinetics of pravastatin in a two-phase, randomized, single-blind, placebo-controlled, crossover study in healthy Chinese male subjects

Deng, Suhua; Chen, Xiaoping; Cao, Dan; Yin, Tongming; Zhou, Dai; Luo, Jian; Tang, Ling; Li, Yuan‐Jian

doi:10.1016/j.clinthera.2009.06.006

Cited by 37 publications

(33 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using the pre+co K i values of rifampicin against OATP1B1 (0.24 μM) and OATP1B3 (0.11 μM) (Table 1), the simulated AUC and C max ratios of rifampicin against pravastatin in a Caucasian population are 2.74 and 2.82 fold (Fig. 6C), respectively, comparable to previously reported AUCR and C max ratio of 2.33 and 2.7, respectively, in a clinical study 37 . DDI prediction of dasatinib against pravastatin was determined assuming that dasatinib only affects OATP1B1 and OATP1B3, which is reasonable as pravastatin only undergoes minor metabolism and has been shown to not interact with typical CYP3A inhibitors such as itraconazole or verapamil 38 .…”

Section: Resultssupporting

confidence: 82%

“…We further used PBPK modeling to evaluate the OATP-mediated DDI potential of dasatinib against pravastatin with rifampicin as the positive control. The simulated pravastatin AUC and C max ratios when co-administered with rifampicin are comparable to that reported previously 37,43 . The prediction from PBPK modelling shows that the AUCR of pravastatin in the presence of dasatinib is 1 even when using the CsA-calibrated K i values (Fig.…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport

Pahwa

Alam

Crowe

et al. 2017

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Current studies determined the effects of pretreatment with rifampicin, an organic anion-transporting polypeptide (OATP) inhibitor, and the tyrosine kinase inhibitor dasatinib on OATP1B1- and OATP1B3-mediated transport, and to evaluate the OATP-mediated drug-drug interaction (DDI) potential of dasatinib using the static R-value and dynamic physiologically-based pharmacokinetic models. Rifampicin and dasatinib pretreatment significantly decreased OATP1B1- and OATP1B3-mediated transport. Rifampicin pretreatment also significantly decreased [3H]-pitavastatin and [3H]-CCK-8 accumulation in human sandwich-cultured hepatocytes. Current studies revealed that estrone-3-sulfate is a less sensitive OATP1B1 substrate than estradiol-17β-glucuronide in assessing rifampicin pretreatment effects. Pretreatment with rifampicin and dasatinib reduced the inhibition constant (Ki) values against OATP1B1 by 3 and 2.1 fold and toward OATP1B3 by 2.4 and 2.1 fold, respectively. The in vitro rifampicin Ki values following pre-incubation are comparable to the estimated in vivo Ki reported previously. Models predict that dasatinib has a low potential to cause OATP1B1- and OATP1B3-mediated DDIs. Time-lapse confocal microscopy demonstrated that rifampicin and dasatinib pretreatment did not affect plasma membrane localization of green-fluorescent protein (GFP)-OATP1B1 and -OATP1B3 in HEK293-GFP-OATP1B1 and -OATP1B3 cells. In summary, we report novel findings that pretreatment with rifampicin and dasatinib potentiates the inhibitory effects toward OATP1B1 and OATP1B3 without affecting plasma membrane levels of the transporters.

show abstract

Section: Resultssupporting

confidence: 82%

Section: Discussionsupporting

confidence: 85%

Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport

Pahwa

Alam

Crowe

et al. 2017

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…A recent study in 12 healthy Asian volunteers found that a single dose of RIF increased pravastatin AUC 0-∞ by 182%, possibly through inhibited hepatic uptake by OATPs and inhibited biliary excretion mediated by MRP2 [58]. However, a multiple-dose study in 10 healthy Caucasian volunteers found that the pravastatin AUC was reduced by 31% [59].…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

et al. 2011

View full text Add to dashboard Cite

Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.

show abstract

“…In humans, pravastatin is eliminated via hepatobiliary and renal excretion mediated by hepatic OATP/MRP2 and renal OAT3, respectively, with minimal metabolism . As a reference, rifampin caused higher increase in exposure of atorvastatin (.8-fold) and pravastatin (;2.5-fold) in humans after a single dose of rifampin (Deng et al, 2009;He et al, 2009). Furthermore, the greater inhibitory potency of telaprevir relative to BOC toward both OATP1B and CYP3A, as demonstrated in the present study, also agrees with clinical DDI results that telaprevir (750 mg, three times daily) increased plasma AUC and C max by 7.88-and 10.6-fold for atorvastatin (Lee et al, 2011), and by 8.96-and 2.86-fold for midazolam (Garg et al, 2012), respectively.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Assessment of Drug-Drug Interaction Potential of Boceprevir Associated with Drug Metabolizing Enzymes and Transporters

et al. 2013

View full text Add to dashboard Cite

The inhibitory effect of boceprevir (BOC), an inhibitor of hepatitis C virus nonstructural protein 3 protease was evaluated in vitro against a panel of drug-metabolizing enzymes and transporters. BOC, a known substrate for cytochrome P450 (P450) CYP3A and aldoketoreductases, was a reversible time-dependent inhibitor (k inact = 0.12 minute 21, K I = 6.1 mM) of CYP3A4/5 but not an inhibitor of other major P450s, nor of UDP-glucuronosyltransferases 1A1 and 2B7. BOC showed weak to no inhibition of breast cancer resistance protein (BCRP), P-glycoprotein (Pgp), or multidrug resistance protein 2. It was a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B1 and 1B3, with an IC 50 of 18 and 4.9 mM, respectively. In human hepatocytes, BOC inhibited CYP3A-mediated metabolism of midazolam, OATP1B-mediated hepatic uptake of pitavastatin, and both the uptake and metabolism of atorvastatin. The inhibitory potency of BOC was lower than known inhibitors of CYP3A (ketoconazole), OATP1B (rifampin), or both (telaprevir). BOC was a substrate for Pgp and BCRP but not for OATP1B1, OATP1B3, OATP2B1, organic cation transporter, or sodium/taurocholate cotransporting peptide. Overall, our data suggest that BOC has the potential to cause pharmacokinetic interactions via inhibition of CYP3A and CYP3A/OATP1B interplay, with the interaction magnitude lower than those observed with known potent inhibitors. Conversely, pharmacokinetic interactions of BOC, either as a perpetrator or victim, via other major P450s and transporters tested are less likely to be of clinical significance. The results from clinical drug-drug interaction studies conducted thus far are generally supportive of these conclusions.

show abstract

Effects of a concomitant single oral dose of rifampicin on the pharmacokinetics of pravastatin in a two-phase, randomized, single-blind, placebo-controlled, crossover study in healthy Chinese male subjects

Cited by 37 publications

References 24 publications

Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport

Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

In Vitro Assessment of Drug-Drug Interaction Potential of Boceprevir Associated with Drug Metabolizing Enzymes and Transporters

Contact Info

Product

Resources

About