Concomitant tacrolimus and micafungin pharmacokinetics in healthy volunteers

被引:70
作者
Hebert, ME
Blough, DK
Townsend, RW
Allison, M
Buell, D
Keirns, J
Bekersky, I
机构
[1] Univ Washington, Dept Pharm, Hlth Sci Ctr H375, Seattle, WA 98195 USA
[2] Fujisawa Healthcare Inc, Deerfield, IL USA
[3] MDS Pharma Serv, Phoenix, AZ USA
关键词
tacrolimus; micafungin; pharmacokinetics; drug interaction;
D O I
10.1177/0091270005279274
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Tacrolimus is an approved immunosuppressive agent and a known substrate for CYP3A. Micafungin is an echinocandin antifungal agent and a mild inhibitor of CYP3A metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of tacrolimus (5 mg oral) and micafungin (100 mg intravenous) alone and with concomitant administration (n=26). Tacrolimus area under the concentration-time curve was 298 center dot 135 mu g.h/L when tacrolimus was administered alone, 305 +/- 129 mu g.h/L (P=.8; confidence interval 89%, 118%) when tacrolimus was given with single-dose micafungin, and 282 +/- 138 mu g.h/L (P=.4; confidence interval 82%,107%) when tacrolimus was given with steady-state micafungin. Despite the mild inhibition of CYP3A in vitro by micafungin, there does not appear to be a drug interaction with tacrolimus and micafungin either with single-dose or steady-state micafungin administration.
引用
收藏
页码:1018 / 1024
页数:7
相关论文
共 15 条
[1]   COMPUTATION OF MODEL-INDEPENDENT PHARMACOKINETIC PARAMETERS DURING MULTIPLE DOSING [J].
BAUER, LA ;
GIBALDI, M .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1983, 72 (08) :978-979
[2]   NONCOMPARTMENTAL DETERMINATION OF THE STEADY-STATE VOLUME OF DISTRIBUTION [J].
BENET, LZ ;
GALEAZZI, RL .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1979, 68 (08) :1071-1074
[3]   In vitro metabolism of cyclosporine A by human kidney CYP3A5 [J].
Dai, Y ;
Iwanaga, K ;
Lin, YS ;
Hebert, MF ;
Davis, CL ;
Huang, WL ;
Kharasch, ED ;
Thummel, KE .
BIOCHEMICAL PHARMACOLOGY, 2004, 68 (09) :1889-1902
[4]  
DAI Y, 2004, INT SOC STUD XEN SEP
[5]  
Dressler D., 1996, Clinical Pharmacology and Therapeutics, V59, P151, DOI 10.1038/sj.clpt.1996.105
[6]  
*FDA, 2001, FDA ADV M CANC CASP
[7]  
*FUJ HEALTHC INC, 2005, MYC MIC SOD INJ PROD
[8]   Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers [J].
Hebert, ME ;
Townsend, RW ;
Austin, S ;
Balan, G ;
Blough, DK ;
Buell, D ;
Keirns, J ;
Bekersky, I .
JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 45 (08) :954-960
[9]   Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism [J].
Lin, YS ;
Dowling, ALS ;
Quigley, SD ;
Farin, FM ;
Zhang, J ;
Lamba, J ;
Schuetz, EG ;
Thummel, KE .
MOLECULAR PHARMACOLOGY, 2002, 62 (01) :162-172
[10]   CYP3A5 polymorphism and the ethnic differences in cyclosporine pharmacokinetics in healthy subjects [J].
Min, DI ;
Ellingrod, VL ;
Marsh, S ;
McLeod, H .
THERAPEUTIC DRUG MONITORING, 2004, 26 (05) :524-528