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. 2021 Jul;41(7):647-652.
doi: 10.1007/s40261-021-01051-4. Epub 2021 Jun 7.

Effect of Omecamtiv Mecarbil on the Pharmacokinetics of Metformin, a Probe Substrate for MATE1/MATE2-K, in Healthy Subjects

Ashit Trivedi  1 , Rajneet K Oberoi  2 , Pegah Jafarinasabian  2 , Hanze Zhang  2 , Marintan Spring  2 , Stephen Flach  3 , Siddique Abbasi  2 , Sandeep Dutta  2 , Edward Lee  2
Affiliations

Effect of Omecamtiv Mecarbil on the Pharmacokinetics of Metformin, a Probe Substrate for MATE1/MATE2-K, in Healthy Subjects

Ashit Trivedi et al. Clin Drug Investig. 2021 Jul.

Abstract

Background and objective: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure with reduced ejection fraction. The objective of this study was to evaluate the potential for OM to affect the pharmacokinetics of metformin.

Methods: This was an open-label, fixed-sequence study in 14 healthy subjects. On Day 1, subjects received an 850 mg oral dose of metformin. From Days 4 to 9, subjects received twice-daily 25 mg oral doses of OM tablets. On Day 10, subjects received an 850 mg oral dose of metformin and a single 25 mg tablet of OM. Blood and urine samples were collected up to 36 h post-dose following administration of metformin on Days 1 and 10 to characterize concentrations of metformin in plasma and urine.

Results: The ratios of the geometric least square means of metformin coadministered with OM compared to metformin alone were 98.7%, 99.3%, and 110.2% for AUCinf, AUClast, and Cmax, respectively. The mean renal clearance of metformin was similar following metformin administered alone (34.2 L/h) compared to metformin coadministered with OM (32.9 L/h). All adverse events were mild in severity and resolved prior to the end of the study. No serious adverse events or treatment-emergent adverse events led to discontinuation from the study.

Conclusions: There was no clinically relevant effect of OM on the pharmacokinetics of metformin in healthy subjects.

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References

    1. Teerlink JR, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med. 2020.
    1. Teerlink JR, et al. Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: rationale and design of GALACTIC-HF. JACC Heart Fail. 2020;8(4):329–40. - DOI
    1. Psotka MA, Teerlink JR. Direct myosin activation by omecamtiv mecarbil for heart failure with reduced ejection fraction. Handb Exp Pharmacol. 2017;243:465–90. - DOI
    1. Malik FI, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011;331(6023):1439–43. - DOI
    1. Kaplinsky E, Mallarkey G. Cardiac myosin activators for heart failure therapy: focus on omecamtiv mecarbil. Drugs Context. 2018;7:212518. - DOI

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