Effects of Single Dose Rifampin on the Pharmacokinetics of Fluvastatin in Healthy Volunteers

Xiang, Yue; Okochi, Hideaki; Kozachenko, Ivan; Sodhi, Jasleen K.; Frassetto, Lynda; Benet, Leslie Z.

doi:10.1002/cpt.2268

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…5 Clinical studies have characterized rifampin mediated reductions in AUC of common oral P-gp probe substrates of up to 30% for digoxin and 67% for dabigatran etexilate. 6 Rifampin has also been shown to inhibit active hepatic uptake of organic anion-transporting polypeptide (OATP) 1B1 and 1B3 (1B1/3) via competitive inhibition, 7,8 and has often been used as a model inhibitor of OATP when given as a single dose. 9 These concurrent inductions and inhibitions of CYP enzymes and various transporters can create complex patterns of DDIs with rifampin for drugs that are substrates of P-gp/CYP3A and OATP1B1/3 where the impact on exposures are dependent on the relative timing of administration.…”

Section: Introductionmentioning

confidence: 99%

“… 5 Clinical studies have characterized rifampin mediated reductions in AUC of common oral P‐gp probe substrates of up to 30% for digoxin and 67% for dabigatran etexilate. 6 Rifampin has also been shown to inhibit active hepatic uptake of organic anion‐transporting polypeptide (OATP) 1B1 and 1B3 (1B1/3) via competitive inhibition, 7 , 8 and has often been used as a model inhibitor of OATP when given as a single dose. 9 …”

Section: Introductionmentioning

confidence: 99%

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Characterizing complex and competing drug–drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine

Kosloski

Wang

et al. 2023

Clinical Translational Sci

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The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N = 12) and a carbamazepine study (N = 12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose. In study 2, GLE 300 mg + PIB 120 mg was administered as a single dose either alone or after multiple doses of carbamazepine 200 mg. Relative to GLE + PIB alone, exposure of GLE was significantly increased by the first co-administered rifampin dose due to OATP inhibition, significantly decreased 24 h after the last rifampin dose due to CYP3A/P-gp induction, and slightly increased when co-administered with steady-state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co-administered with the first rifampin dose but was significantly decreased with steady-state rifampin co-administration, or 24 h after the last rifampin dose due to P-gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P-gp induction. The regimens tested were generally well-tolerated by the subjects and no new safety issues were identified. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Rifampin single-dose inhibits OATP1B1/3 transport and when given over multiple days induces P-gp transport and CYP3A metabolism. Carbamazepine also induces P-gp and CYP3A with multiple dosing. Advanced clinical study designs allow identification of rifampin mediated drug-drug interactions (DDIs) due to inhibition versus induction. The direct acting antivirals glecaprevir (GLE) and F I G U R E 1 Study design schematics for drug-drug interaction studies of GLE and pibrentasvir with rifampin (study 1) or with carbamazepine (study 2

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterizing complex and competing drug–drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine

Kosloski

Wang

et al. 2023

Clinical Translational Sci

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“…BA (Kobayashi et al, 2004;Shen et al, 2015b) and RFP (Zhou et al, 2016;Xiang et al, 2021) are commonly used inhibitors of MCT1 and OATP, respectively. Referring to the literature works, we selected 10 mmol•L −1 BA and 50 μmol•L −1 RFP for the bidirectional transport experiments.…”

Section: Effect Of Transporters On Bidirectional Transport Of Tdsmentioning

confidence: 99%

Pharmacokinetics and absorption mechanism of tandospirone citrate

Li,

Chen,

Jia

et al. 2023

Front. Pharmacol.

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Tandospirone citrate (TDS) is commonly used for the treatment of patients with generalized anxiety disorder in clinical practice, and several studies are developing new indications for TDS. However, the in vivo processes and absorption properties of TDS have not been systematically investigated. In this work, we conducted a comprehensive investigation using in vivo, in vitro, and ex vivo approaches, involving animal and cellular models, to examine the pharmacokinetic properties and absorption mechanisms of TDS. The results of in vivo studies revealed that the half-life (t1/2) of TDS was 1.380 ± 0.46 h and 1.224 ± 0.39 h following intragastric (i.g.) and intravenous (i.v.) administration of 20 mg/kg TDS, respectively. This indicates that TDS is rapidly eliminated in rats. The area under the curve (AUC) of TDS after i.g. and i.v. administration was 114.7 ± 40 ng/mL*h and 48,400 ± 19,110 ng/mL*h, respectively, and the absolute bioavailability of TDS was found to be low (0.24%). Furthermore, TDS was extensively metabolized in rats, with the AUC of the major active metabolite [1-[2-pyrimidyl]-piperazine] being approximately 16.38-fold higher than that of TDS after i.g. administration. The results from the in vitro Caco-2 cell model and ex vivo everted gut sac experiment demonstrated that TDS exhibited good permeability, and its transport was influenced by concentration, temperature, and pH. Passive diffusion was identified as the main absorption mechanism. In conclusion, TDS is classified as a Biopharmaceutics Classification System (BCS) class I drug, characterized by high solubility and permeability. The low absolute bioavailability of TDS may be attributed to its rapid metabolism. The pharmacokinetic data and absorption characteristics obtained in this study provide fundamental information for the further development and utilization of TDS.

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Mechanistic Account of Distinct Change in Organic Anion Transporting Polypeptide 1B (OATP1B) Substrate Pharmacokinetics during OATP1B-Mediated Drug-Drug Interactions Using Physiologically Based Pharmacokinetic Modeling

Hegde,

Morse

2024

Drug Metab Dispos

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Commonly used abbreviations: area under the plasma concentration-time curve (AUC), bioavailability (F), clearance (CL), drug-drug interaction (DDI), intravenous (IV), maximum concentration (C max ), mean residence time (MRT), physiologically-based pharmacokinetics (PBPK), organic anion transporting polypeptide (OATP) List of non-standard abbreviations: enterohepatic cycling (EHC), extraction ratio (ER), extended clearance model (ECM), noncompartmental analysis (NCA), single dose (SD), steady-state This article has not been copyedited and formatted. The final version may differ from this version.

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Effects of Single Dose Rifampin on the Pharmacokinetics of Fluvastatin in Healthy Volunteers

Cited by 3 publications

References 26 publications

Characterizing complex and competing drug–drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine

Characterizing complex and competing drug–drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine

Pharmacokinetics and absorption mechanism of tandospirone citrate

Mechanistic Account of Distinct Change in Organic Anion Transporting Polypeptide 1B (OATP1B) Substrate Pharmacokinetics during OATP1B-Mediated Drug-Drug Interactions Using Physiologically Based Pharmacokinetic Modeling

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