Safety, pharmacokinetics, and food-effect of pivmecillinam after single- and multiple-dose in healthy Chinese subjects: a phase I study.

Autor: Zhang LL; School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China., Liu Y; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China., Huang QY; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China., Zhang HW; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China., Xie LJ; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China., Chen J; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China., Ding L; Department of Pharmaceutical Analytical, China Pharmaceutical University, Nanjing, 210009, China., Zhou C; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China., Sun LN; School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. sunluning0521@aliyun.com.; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. sunluning0521@aliyun.com., Wang YQ; School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. wyqjsph@163.com.; Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. wyqjsph@163.com.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct; Vol. 397 (10), pp. 7639-7647. Date of Electronic Publication: 2024 May 01.
DOI: 10.1007/s00210-024-03118-3
Abstrakt: Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections. The purpose of this study was to assess the safety, and pharmacokinetics of pivmecillinam and mecillinam after single- and multiple-dose oral administration of pivmecillinam tablets in healthy Chinese subjects. The study also investigated the profile of urinary excretion of mecillinam, as well as the effect of food and gender on the pharmacokinetics of pivmecillinam and mecillinam. This study was a single-center, open-label phase I study carried out in three groups. In total, 34 subjects were included in the study: group 1-food effect study with pivmecillinam 200 mg (n = 12); group 2-single- and multiple-dose study with pivmecillinam 400 mg (n = 12); group 3-single dose study with pivmecillinam 600 mg (n = 10). The plasma and urine concentrations of pivmecillinam and mecillinam were measured, and their pharmacokinetics were calculated. Treatment-emergent adverse events were evaluated and recorded in safety assessments for three groups. No severe adverse events were found in this study. After a single dose of pivmecillinam was taken orally, the maximum plasma concentration (C max ) and the area under the concentration-time curve (AUC) of pivmecillinam increased in a dose-proportional manner, nor did mecillinam. Food had significant effects on C max and AUC 0-t of pivmecillinam and C max of mecillinam. The mean cumulative percentage of urine excretion of mecillinam at 0 to 24 h ranged from 35.5 to 44.0%. Urinary cumulative excretion is relative to the drug dose, but the diet and multiple-dose administration did not affect the urinary cumulative excretion rate. The safety and pharmacokinetics of pivmecillinam and mecillinam after single- (200/400/600 mg) or multiple-dose (400 mg) administration were demonstrated in healthy Chinese subjects. Food affected the pharmacokinetics of pivmecillinam and mecillinam.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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