Population pharmacokinetic analysis of micafungin in Japanese patients with fungal infections.
The object of this analysis was to develop a population pharmacokinetic model of micafungin, a new anti-fungal agent of the echinocandin class, to optimize dosing in Japanese patients with fungal infections. Population pharmacokinetics parameters were determined using NONMEM based on pharmacokinetic data from 198 subjects in seven clinical studies, comprising four phase I, two phase II and one pediatric phase III study. The healthy subjects received intravenous infusion of 2.5-150 mg micafungin. Adult and pediatric patients, age range of 8 month to 15 yeras old, were received 25-150 mg and 1-6 mg/kg daily, respectively. A total of 1825 micafungin plasma samples were available for this analysis. Two-compartment pharmacokinetic model was adopted. The clearance of micafungin was influenced by body weight in children and platelet counts (PLT). However the PLT accounted for less than 20% of the variation of micafungin clearance in Japanese subjects. In conclusions, body weight is the primary covariate factor in pediatric patients. The dose adjustment by body weight would be required only pediatric patients for the micafungin therapy in Japanese patients with fungal infection.
Tabata
Kenji
K
Analysis & Pharmacokinetics Research Labs., Astellas Pharma. Inc., Analysys and Pharmaco Kinetics Labs, Drug Discovery, Tsukuba-city, Ibaraki, Japan. kenji.tabata@astellas.com
Katashima
Masataka
M
Kawamura
Akio
A
Kaibara
Atsunori
A
Tanigawara
Yusuke
Y
D000328:Adult; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D044466:Asian People; D001499:Bayes Theorem; D001835:Body Weight; D002648:Child; D054714:Echinocandins; D006801:Humans; D007564:Japan; D055666:Lipopeptides; D008074:Lipoproteins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D008954:Models, Biological; D009181:Mycoses / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013997:Time Factors
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin