Pharmacokinetics of sunitinib malate in subjects with hepatic impairment

This study evaluated the effect of hepatic impairment on the pharmacokinetics of sunitinib and its active metabolite, SU12662. This open-label study enrolled subjects with normal hepatic function ( n  = 8), mild (Child–Pugh [CP]-A; n  = 8), or moderate (CP-B; n  = 8) hepatic impairment. Subjects rec...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2010-09, Vol.66 (4), p.699-707
Main Authors: Bello, Carlo L., Garrett, May, Sherman, Laurie, Smeraglia, John, Ryan, Bob, Toh, Melvin
Format: Article
Language:English
Subjects:
Aged
Alanine Transaminase - blood
Antineoplastic agents
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacokinetics
Area Under Curve
Biological and medical sciences
Cancer Research
Endpoint Determination
Female
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Indoles - adverse effects
Indoles - pharmacokinetics
Liver Diseases - metabolism
Liver Function Tests
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Oncology
Original Article
Other diseases. Semiology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pyrroles - adverse effects
Pyrroles - pharmacokinetics
Sample Size
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Summary:This study evaluated the effect of hepatic impairment on the pharmacokinetics of sunitinib and its active metabolite, SU12662. This open-label study enrolled subjects with normal hepatic function ( n  = 8), mild (Child–Pugh [CP]-A; n  = 8), or moderate (CP-B; n  = 8) hepatic impairment. Subjects received sunitinib 50 mg as a single oral dose. Mild or moderate hepatic impairment did not significantly alter sunitinib, SU12662, or total drug (TD) systemic exposure. In subjects with normal hepatic function, mild, or moderate hepatic impairment, respectively, TD AUC 0–∞ was 1,938, 2,002, and 1,999 ng h/ml, TD AUC 0–last was 1,913, 1,956, and 1,958 ng h/ml, and TD C max was 26.0, 27.3, and 26.7 ng/ml. There were no other notable pharmacokinetic differences and sunitinib was well tolerated. The pharmacokinetic findings of this study do not indicate a need to adjust the currently approved starting dose of sunitinib (50 mg daily on Schedule 4/2) for cancer patients with mild to moderate liver impairment.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-009-1213-4