Effects of hepatic CYP3A4 activity on disposition of micafungin in liver transplant recipients with markedly small-for-size grafts.
Micafungin, the first candin antifungal drug developed in Japan, has a significant therapeutic effect against deep-seated mycoses caused by Candida or Aspergillus. Little is known, however, about the optimal dosage or disposition of micafungin in patients with severe hepatic impairment. Nine liver transplant recipients (5 males and 4 females) were enrolled in this study. In 1 recipient with a markedly small-for-size graft (ratio of graft volume to standard liver volume at the time of transplantation: 25.9%), the areas under the plasma concentration-time curves up to 12 hours postdose (AUC(0-12 h)) at doses of 50 and 100 mg/d were 79.38 and 601.17 mug.h/mL, respectively. The corresponding elimination half-life (T(1/2)) values were 16.01 and 75.75 hours, and saturated elimination was observed only at the dose of 100 mg/d. The mean urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) in the small-for-size graft recipient was significantly (P < .05) lower than that in the other recipients. In conclusion, graft size was an important factor affecting disposition of micafungin. For liver transplant recipients with markedly small-for-size grafts, the optimal dosage of micafungin to reach and maintain therapeutic plasma levels is estimated to be 50 mg/d.
Mochizuki
N
N
Department of Medication Use Analysis and Clinical Research Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
Matsumoto
K
K
Ohno
K
K
Shimamura
T
T
Furukawa
H
H
Todo
S
S
Kishino
S
S
D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001228:Aspergillosis / Q000517:prevention & control; D002177:Candidiasis / Q000517:prevention & control; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D054714:Echinocandins; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008099:Liver / Q000033:anatomy & histology* / Q000201:enzymology*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D000077551:Micafungin; D009929:Organ Size; D010456:Peptides, Cyclic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000382:microbiology / Q000517:prevention & control; D011184:Postoperative Period
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077551:Micafungin