Vol.68 No.S-1 November 2020

Effect of lascufloxacin on the plasma concentrations of theophylline in healthy volunteers

Yoshihito Niki¹⁾, Takehiko Sanbe²⁾, Noriko Hida²⁾, Shigeru Manita³⁾ and Naoki Uchida²⁾

¹⁾Division of Clinical Infectious Diseases, Department of Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan
²⁾Department of Pharmacology, Showa University School of Medicine
³⁾Watarase Research Center, Kyorin Pharmaceutical Co., Ltd.

Abstract

The effect of lascufloxacin (LSFX) on the plasma concentrations of theophylline was studied in 6 healthy male volunteers. Initially, 200 mg theophylline was given orally twice daily for 4 days prior to the start of LSFX administration. Then, from Day 5 to Day 11, 150 mg LSFX was given orally once daily for 7 days, along with theophylline. In this study, the plasma concentrations of theophylline were measured on Day 4, Day 8 (the 4th day of co-administration) and Day 11 (the 7th day of co-administration). The pharmacokinetic parameters on Day 8 and Day 11 were assessed using the parameters recorded on Day 4 as the control plasma level in theophylline monotherapy.
The mean plasma concentrations of theophylline on Day 4, Day 8, and Day 11 remained 8.32-8.98, 8.96-9.95, and 9.61-10.5 μg/mL at each time of blood collection until 10 hours after the administration. The mean C_max values of theophylline on Day 4, Day 8, and Day 11 were 9.46, 10.3 and 10.8 μg/mL, and the AUC_0-10 values were 87.1, 95.8 and 101 μg・h/mL, respectively. The t_max was 4-5 hours at all the time points. The mean plasma concentration of theophylline was higher on Day 8 and Day 11 than on Day 4, and was slightly higher on Day 11 than on Day 8. During concurrent administration of both drugs, the C_max of theophylline increased by 14% and its AUC_0-10 increased by 16% on Day 11 as compared to the values recorded on Day 4. By subject, the C_max of theophylline increased from 9% to 56%, and its AUC_0-10 increased from 12% to 55% in 4 subjects on Day 11, whereas no changes in the plasma pharmacokinetic parameters of theophylline were observed in 2 subjects. Only one adverse event, namely, neutropenia, was observed in one subject, and the event was judged as mild.
It was concluded that from the viewpoint of safety, there is no need to adjust the dose of LSFX when this drug needs to be administered in combination with theophylline.

Key word

lascufloxacin, theophylline, drug-drug interaction

Received

October 30, 2019

Accepted

May 14, 2020

Jpn. J. Chemother. 68 (S-1): 32-40, 2020