Pharmacokinetic Drug–drug Interaction Study between Raltegravir and Citalopram

Blonk, Maren I.; Langemeijer, Charlotte Ca; Colbers, Angela; Hoogtanders, K.; Schaik, Ron H.N. van; Schouwenberg, B.J.J.W.; Burger, David M.

doi:10.3851/imp2993

Cited by 7 publications

(11 citation statements)

References 37 publications

(46 reference statements)

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“…5 Coadministration of tenofovir was also shown to result in modest increases in raltegravir concentrations that were not clinically meaningful. 9 Raltegravir has a long occupancy time on the viral integrase. 6 Rifampin decreased mean raltegravir trough levels (C 12 hr ) by 61%, consistent with a clinically meaningful reduction.…”

mentioning

confidence: 99%

“…8 In a recent publication, raltegravir did not alter the pharmacokinetics of citalopram and desmethylcitalopram, and citalopram also did not alter the pharmacokinetics of raltegravir to a clinically meaningful extent. 9 Raltegravir has a long occupancy time on the viral integrase. 10,11 Once bound, raltegravir remains in the active site of the HIV-1 integrase protein for a long time, demonstrating a dissociative half-life ranging from 7.3 11 to 8.8 10 hours.…”

mentioning

confidence: 99%

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Single‐ and Multiple‐Dose Pharmacokinetics of Once‐Daily Formulations of Raltegravir

Krishna

Rizk

Larson

et al. 2017

Clinical Pharm in Drug Dev

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A new once-daily formulation of raltegravir, an integrase strand transfer inhibitor indicated in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus-1 infection, is under development. Single-dose and steady-state pharmacokinetics of 1200 mg for 2 formulations of raltegravir were characterized in 2 open-label phase 1 studies in healthy male and female subjects aged 18 to 55 years. The new raltegravir 600-mg formulation had a higher relative bioavailability compared with the 400-mg tablets. Once absorbed, both 3 × 400-mg and 2 × 600-mg dosage forms of raltegravir exhibited similar systemic pharmacokinetics; in dictating bioavailability, differences were from increased absorption that was the result of improved in vivo disintegration/dissolution. Food had a smaller effect on the pharmacokinetics of raltegravir when given as 2 × 600-mg formulation (42% vs 73% decrease in AUC ). Steady state was generally reached in 2 days, with little to no accumulation with multiple-dose administration. Raltegravir 1200 mg was found to exhibit pharmacokinetic properties amenable for once-daily dosing and was generally well tolerated in healthy subjects after single and multiple doses. The new formulation improved the bioavailability of this Biopharmaceutics Classification System class II compound.

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confidence: 99%

mentioning

confidence: 99%

Single‐ and Multiple‐Dose Pharmacokinetics of Once‐Daily Formulations of Raltegravir

Krishna

Rizk

Larson

et al. 2017

Clinical Pharm in Drug Dev

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“…Data from 11 pharmacokinetic studies with raltegravir and rich sampling schedules were pooled 8,10,14–21 . These studies include a combination of healthy and HIV‐infected subjects taking 400 mg and 600 mg raltegravir tablets, and pregnant subjects taking the 400 mg tablets.…”

Section: Methodsmentioning

confidence: 99%

“…These studies include a combination of healthy and HIV‐infected subjects taking 400 mg and 600 mg raltegravir tablets, and pregnant subjects taking the 400 mg tablets. The study protocols and subject characteristics are summarized in Table 1, and detailed information can be found in the original publications 8,10,14–21 . Twenty‐two European, HIV‐infected, pregnant women treated with a 400 mg b.i.d.…”

Section: Methodsmentioning

confidence: 99%

“…The study protocols and subject characteristics are summarized in Table 1, and detailed information can be found in the original publications. 8,10,[14][15][16][17][18][19][20][21] Twenty-two European, HIVinfected, pregnant women treated with a 400 mg b.i.d. raltegravir-based regimen were included to determine the effect of pregnancy on the pharmacokinetics of raltegravir.…”

Section: Pharmacokinetic Datamentioning

confidence: 99%

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A population pharmacokinetics analysis assessing the exposure of raltegravir once‐daily 1200 mg in pregnant women living with HIV

Bukkems¹,

Post²,

Burger³

et al. 2021

CPT Pharmacom & Syst Pharma

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A drug–drug interaction study to evaluate the impact of peficitinib on OCT1- and MATE1-mediated transport of metformin in healthy volunteers

Shibata

Toyoshima

Kaneko

et al. 2020

Eur J Clin Pharmacol

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Purpose Peficitinib is an oral pan-Janus kinase inhibitor for the treatment of rheumatoid arthritis. Co-administration of peficitinib with metformin, a type 2 diabetes therapy, can occur in clinical practice. Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K. This study investigated the effect of peficitinib on metformin pharmacokinetics in vitro and in healthy volunteers. Methods Inhibitory effects of peficitinib and its metabolite H2 on metformin uptake into human OCT1/2- and MATE1/2-K-expressing cells were assessed in vitro. In an open-label, drug–drug interaction study, 24 healthy volunteers received a single dose of metformin 750 mg on Days 1 and 10, and a single dose of peficitinib 150 mg on Days 3 and 5–11. Blood and urine samples were collected pre-dose on Days 1 and 10, and at intervals ≤ 48 h post-dose. Metformin concentration was determined by liquid chromatography–tandem mass spectrometry and its pharmacokinetic parameters calculated. Results Peficitinib, but not H2, inhibited metformin uptake into OCT1- and MATE1/2-K-expressing cells. Repeated-dose administration of peficitinib reduced metformin area under the concentration–time curve from 0 h extrapolated to infinity (AUC inf ) by 17.4%, maximum plasma concentration (C max ) by 17.0%, and renal clearance (CL R ) by 12.9%. Co-administration of peficitinib with metformin was generally well tolerated. Conclusion Slight changes in AUC inf , C max and CL R of metformin were observed when co-administered with peficitinib; however, these changes were considered not clinically relevant. Electronic supplementary material The online version of this article (10.1007/s00228-020-02876-2) contains supplementary material, which is available to authorized users.

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Pharmacokinetic Drug–drug Interaction Study between Raltegravir and Citalopram

Cited by 7 publications

References 37 publications

Single‐ and Multiple‐Dose Pharmacokinetics of Once‐Daily Formulations of Raltegravir

Single‐ and Multiple‐Dose Pharmacokinetics of Once‐Daily Formulations of Raltegravir

A population pharmacokinetics analysis assessing the exposure of raltegravir once‐daily 1200 mg in pregnant women living with HIV

A drug–drug interaction study to evaluate the impact of peficitinib on OCT1- and MATE1-mediated transport of metformin in healthy volunteers

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