Pharmacokinetics-pharmacodynamics of micafungin in Japanese patients with deep-seated mycosis.
The objective of this study was to describe the pharmacokinetic profile and investigate the effective concentration of micafungin in Japanese male patients with deep-seated mycosis. 66 patients were treated with i.v. micafungin 12.5-150 mg intravenously for up to 56 days. At this dose range, micafungin showed linear pharmacokinetics, and the mean values of Cmax and Cmin amounted to 3.16-12.9 microg/mL and 0.70-3.68 microg/mL, respectively. The mean value for the elimination half-life was 13.5 h (95 samples from 65 patients), and it remained almost constant over the dose range. In addition, the elimination half-life was not influenced by age, gender or weight, and was similar to that found in healthy subjects. The active metabolites M1 and M2 were detectable, but their exposure was lower than that of the unchanged drug. The pharmacokinetic-pharmacodynamics ob micafungin were then investigated. The overall clinical response rate against aspergillosis and candidiasis showed good results at a dose of 50 mg and over. The Cmax and Cmin at the latter dose amounted to 5.16 and 1.41 microg/mL, respectively. In conclusion, micafungin showed linear pharmacokinetics at doses ranging from 12.5 to 150 mg, and the effective concentration was considered to be over 5 microg/mL as maximum level in Japanese patients with deep-seated mycosis such as candidiasis and aspergillosis.
Tabata
Kenji
K
Analysis & Pharmacokinetics Research Laboratories, Astellas Pharma Inc., Tsukuba-city, Ibaraki, Japan.
Katashima
Masataka
M
Kawamura
Akio
A
Kagayama
Akira
A
Kohno
Shigeru
S
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy*; D002177:Candidiasis / Q000175:diagnosis / Q000188:drug therapy*; D054714:Echinocandins; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012720:Severity of Illness Index
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin