Anidulafungin Does Not Require Dosage Adjustment in Subjects With Varying Degrees of Hepatic or Renal Impairment

Journal of Clinical Pharmacology - Tập 47 Số 4 - Trang 461-470 - 2007
James A. Dowell1,2, Martin Stogniew2,3, David Krause4,2, Bharat Damle5
1Shire Pharmaceuticals Inc, Wayne, Pennsylvania
2Vicuron Pharmaceuticals, a subsidiary of Pfizer, Inc, New York
3Zelos Therapeutics, Inc, West Conshohocken, Pennsylvania.
4Delta Pharmaceutical Consulting, LLC.
5Pfizer Global Research and Development, Pfizer, Inc, New York.

Tóm tắt

Two open‐label studies assessed the effects of hepatic and renal impairment on anidulafungin pharmacokinetics. A single 50‐mg dose was administered intravenously to subjects with varying degrees of hepatic or renal insufficiency or with end‐stage renal disease; all were matched to normal healthy controls. Anidulafungin was well tolerated. AUC, CL, Cmax, tmax, t1/2, and Vss between renally impaired subjects and controls were not significantly different (P .05), and no measurable amounts of drug were found in dialysate. The same pharmacokinetic parameters were also not affected (P .05) by mild or moderate hepatic insufficiency, with respective mean AUCs of 50.6 ± 11.7 μg·h/mL and 68.6 ± 14.5 μg·h/mL, compared to 70.0 ± 13.4 μg·h/mL in controls. Statistically significant decreases (P < 05) of AUC (33% change) and Cmax (36% change) in severely hepatically impaired subjects compared to controls—most likely secondary to ascites and edema—were not clinically relevant. Anidulafungin can be safely administered to patients with any degree of hepatic or renal impairment without dosage adjustment and without regard to hemodialysis schedules.

Từ khóa


Tài liệu tham khảo

10.1016/S0140-6736(03)14472-8

10.1128/AAC.47.10.3149-3154.2003

10.1016/S0732-8893(02)00507-2

10.1093/clinids/19.Supplement_1.S49

Marty F, 2002, Antifungal use in HIV infection, Expert Opin Pharmacother, 49, 37

10.1080/00365540110077470

ThyeD ShepherdB WhiteRJ WestonHE HenkelI.Anidulafungin: a phase I study to identify the maximum tolerated dose in healthy volunteers [abstract A‐36]. Poster presented at: ICAAC;December 1619 2001; Chicago Ill.

10.1177/0091270004265644

Stogniew M, 2003, Anidulafungin biotransformation in humans by degradation not metabolism, Clin Microbiol Infect, 9, 291

10.1177/0091270004270146

Eraxis (anidulafungin) for injection, 2006, US prescribing information

10.1177/0091270004270146

10.1002/bjs.1800600817

10.1159/000180580

US Department of Health and Human Services, Food and Drug Administration, 2003, Guidance for Industry—Pharmacokinetics in Patients With Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling

US Department of Health and Human Services, Food and Drug Administration, 1998, Guidance for Industry—Pharmacokinetics in Patients With Impaired Renal Function: Study Design, Data Analysis, and Impact on Dosing and Labeling

Brown GL, 1720, Phase I dose optimization study for V‐echinocandin [abstract 1105]

10.1007/s10096-004-1228-z

AndesD MarchilloK.In vivo pharmacodynamic characterization of a new echinocandin anidulafungin againstCandida albicansandCandida glabratain the neutropenic murine disseminated candidiasis model [abstract A‐1109]. Poster presented at: ICAAC;September 2730 2006; San Francisco Calif.

10.1086/424465

10.1128/AAC.00507-06

Cancidas (caspofungin acetate) for injection, 2005, US prescribing information

StoneJ HollandS LiS et al.Effect of hepatic insufficiency on the pharmacokinetics of caspofungin [abstract A‐14]. Poster presented at: ICAAC; December 16–19 2001; Chicago Ill.

Mycamine (micafungin sodium) for injection, 2005, US prescribing information

Krause D, 2003, Safety results from a phase 3, randomized, double‐blind, double‐dummy study of anidulafungin (ANID) vs. fluconazole (FLU) in patients with esophageal candidiasis (EC) [abstract 36]

10.1586/14787210.2.4.499

10.1086/376523

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Thông tin xuất bản

Journal of Clinical Pharmacology

Tập 47 Số 4

461-470

Thông tin tác giả