Effect of renal function on the pharmacokinetics of fimasartan: a single-dose, open-label, Phase I study

Abstract

Background

Fimasartan is a novel angiotensin II receptor blocker. Fimasartan is mainly eliminated via biliary excretion, and its urinary elimination is less than 3%.

Objective

Based on guidance from the United States Food and Drug Administration, a reduced pharmacokinetic (PK) study was conducted to evaluate the effect of renal function on the PK of fimasartan in patients with renal impairment and healthy volunteers.

Methods

A single centre, single-dose, open-label, healthy volunteer controlled trial was conducted in patients with renal impairment (RI) (estimated glomerular filtration rate lower than 30 mL/min/1.73 m²) and age-, weight- and sex-matched healthy volunteers (estimated glomerular filtration rate higher than 90 mL/min/1.73 m²). All participants received a single oral dose of fimasartan 120 mg, after which serial blood sampling for PK evaluation was conducted. Noncompartmental PK analysis of fimasartan was performed. A mixed-effects model approach was used to identify significant covariates and PK parameters.

Results

Sixteen subjects were enrolled (8 healthy volunteers and 8 RI patients). The maximum plasma concentrations and areas under the plasma concentration curves of the RI patients were higher than those of the healthy volunteers, with geometric mean ratios of 1.87 and 1.73, respectively. The relative bioavailability of fimasartan from the population PK analysis was 77% higher in the RI patients than in the healthy volunteers.

Conclusion

The increased drug exposure of fimasartan in RI patients was explained by the increased relative bioavailability. This result can be explained from our knowledge concerning alterations in PK related to renal function.

Keywords:

• renal impairment
• fimasartan
• pharmacokinetics
• safety

Acknowledgments

This study was sponsored by Boryung Pharmaceutical Co., Ltd., Seoul, Korea. This study was designed and conducted by qualified investigators of the Department of Clinical Pharmacology and Therapeutics of Seoul National University College of Medicine and Hospital. The sponsor played a minor role in study design and interpretation. All of the coauthors participated in either writing or reviewing the manuscript.

Disclosure

The authors report no conflicts of interests regarding the content of this article.