Dataset Information

Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open-label, drug-drug interaction study.

ABSTRACT:

Aims

The primary aim of this study was to assess the individual effects of probenecid and cimetidine on mirogabalin exposure.

Methods

This phase 1, open-label, crossover study randomized healthy adults to receive three treatment regimens, each separated by ?5-day washout: a single oral dose of mirogabalin 15 mg on day 2, mirogabalin 15 mg on day 2 plus probenecid 500 mg every 6 h from days 1 to 4, and mirogabalin 15 mg on day 2 plus cimetidine 400 mg every 6 h from days 1 to 4.

Results

Coadministration of mirogabalin with probenecid or cimetidine increased the maximum and total mirogabalin exposure. The geometric mean ratios of C_max and AUC_(0-t) (90% CI) with and without coadministration of probenecid were 128.7% (121.9-135.7%) and 176.1% (171.9-180.3%), respectively. The geometric mean ratios of C_max and AUC_(0-t) (90% CI) with and without coadministration of cimetidine were 117.1% (111.0-123.6%) and 143.7% (140.3-147.2%), respectively. Mean (standard deviation) renal clearance of mirogabalin (l h^-1 ) was substantially slower after probenecid [6.67 (1.53)] or cimetidine [7.17 (1.68)] coadministration, compared with mirogabalin alone [11.3 (2.39)]. Coadministration of probenecid or cimetidine decreased mirogabalin mean (standard deviation) apparent total body clearance [10.5 (2.33) and 12.8 (2.67) l h^-1 , respectively, vs. 18.4 (3.93) for mirogabalin alone].

Conclusions

A greater magnitude of change in mirogabalin exposure was observed when coadministered with a drug that inhibits both renal and metabolic clearance (probenecid) vs. a drug that only affects renal clearance (cimetidine). However, as the increase in exposure is not clinically significant (>2-fold), no a priori dose adjustment is recommended.

SUBMITTER: Tachibana M

PROVIDER: S-EPMC6138503 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open-label, drug-drug interaction study.

Tachibana Masaya M Yamamura Naotoshi N Atiee George J GJ Hsu Ching C Warren Vance V He Ling L Dishy Victor V Zahir Hamim H

British journal of clinical pharmacology 20180809 10

<h4>Aims</h4>The primary aim of this study was to assess the individual effects of probenecid and cimetidine on mirogabalin exposure.<h4>Methods</h4>This phase 1, open-label, crossover study randomized healthy adults to receive three treatment regimens, each separated by ≥5-day washout: a single oral dose of mirogabalin 15 mg on day 2, mirogabalin 15 mg on day 2 plus probenecid 500 mg every 6 h from days 1 to 4, and mirogabalin 15 mg on day 2 plus cimetidine 400 mg every 6 h from days 1 to 4.<h4 ...[more]

PMID: 29920736

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Dataset Information

Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open-label, drug-drug interaction study.

Aims

Methods

Results

Conclusions

Publications

Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open-label, drug-drug interaction study.

Similar Datasets

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