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Effect of Hepatic Impairment on the Pharmacokinetics of Pasireotide (SOM230): Results From a Multicenter Phase I Study
Author(s) -
Horsmans Yves,
Hu Ke,
Ruffin Matthieu,
Wang Ying,
Song Dongweon,
Bouillaud Emmanuel,
Wang Yanfeng,
Mazur Dago,
Botha FransPeter,
Heuman Douglas M.
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011400072
Subject(s) - pasireotide , medicine , acromegaly , adverse effect , pharmacokinetics , gastroenterology , somatostatin , hepatic function , growth hormone , hormone
Pasireotide is a novel, multireceptor‐targeted somatostatin analogue with high affinity for sst 1,2,3 and sst 5 under clinical evaluation in tumors of neuroendocrine origin, including Cushing's disease, acromegaly, and neuroendocrine tumors. In this phase I, open‐label, multicenter study, the pharmacokinetics and safety of a single subcutaneous (SC) injection of pasireotide 600 μg were evaluated in adults with normal hepatic function (n = 15) and mild (n = 6), moderate (n = 7), or severe hepatic impairment (n = 6). Following a single dose of pasireotide SC 600 μg, there were no significant differences in the plasma exposure of pasireotide between participants with normal hepatic function or mild hepatic impairment. Subjects with moderate and severe hepatic impairment showed an increase in AUC ∞ by 56% and 42%, respectively; this increase was 60% and 79% respectively, after adjusting for differences in age, BMI, and baseline serum albumin level between treatment groups. The incidence and severity of adverse events were similar across cohorts, with no clinically relevant differences in type or frequency of adverse events between cohorts. In conclusion, a single dose of pasireotide SC 600 μg was well tolerated in subjects with hepatic impairment. Drug exposure in subjects with mild hepatic impairment was similar to that seen in healthy volunteers, whereas subjects with moderate and severe hepatic impairment experienced higher exposure to pasireotide. Adjustment of the pasireotide dose may be required for patients with moderate and severe hepatic impairment.