Vol.68 No.S-1 November 2020

Pharmacokinetics of lascufloxacin in patients with hepatic impairment

Takeshi Okanoue¹⁾, Toshihide Shima¹⁾, Fumiko Minami²⁾, Saiyu Tanaka³⁾, Shiro Takami⁴⁾ and Shigeru Manita⁵⁾

¹⁾Department of Gastroenterology, Saiseikai Suita Hospital, 1-2 Kawazono, Suita, Osaka, Japan
²⁾Daiwakai Daiwa Hospital
³⁾Center for Digestive and Liver Disease, Nara City Hospital
⁴⁾Department of Gastroenterology, Otsu Municipal Hospital
⁵⁾Watarase Research Center, Kyorin Pharmaceutical Co., Ltd.

Abstract

We investigated the safety profiles, as well as the effects of impaired liver function on the pharmacokinetics (PK) of lascufloxacin (LSFX) in 13 Japanese male and female volunteers with mild (11 subjects) or moderate (2 subjects) hepatic impairment (hereafter simply, hepatic impairment) classified by the Child-Pugh score. Each subject received a single oral dose of 75 mg LSFX in the fasting state. The plasma concentrations of LSFX and its descyclopropyl form (a metabolite) were determined by a HPLC method, and the PK parameters were calculated.
The mean peak plasma concentrations in the subjects with mild and moderate hepatic impairment cases were 0.862 μg/mL at 1.31 hours and 1.03 μg/mL at 0.999 hours. The mean elimination half-lives were 15.5 and 21.5 hours, with AUC_inf values of 14.4 and 18.8 μg・h/mL and CL/F values of 5.77 and 4.51 L/h, respectively. The plasma concentrations of the descyclopropyl form of the drug as compared to LSFX remained less than 1/10-1/5 in the subjects with mild hepatic impairment and 1/20-1/5 in the subjects with moderate hepatic impairment. There were no apparent differences in the plasma concentrations of LSFX or its descyclopropyl form between the subjects with mild and moderate hepatic impairment. The PK parameters were also considered not to be significantly different from those observed in healthy adults in a separate study. There were no adverse reactions, or abnormalities of the clinical laboratory findings, vital signs or ECG in the subjects, except for mild constipation in one subject.
We concluded that dose adjustment of LSFX is unnecessary for clinical cases with mild hepatic impairment, since mild hepatic impairment had little effects on the PK profile of LSFX or its metabolite. However, careful administration of the drug would be advisable in patients with moderate or severe hepatic impairment, because of the very limited clinical experience.

Key word

lascufloxacin, hepatic failure, pharmacokinetics, clinical trial

Received

October 30, 2019

Accepted

May 14, 2020

Jpn. J. Chemother. 68 (S-1): 24-31, 2020