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Effect of verapamil on the pharmacokinetics of pasireotide in healthy volunteers
Author(s) -
Kornberger Ruediger,
Ting Lillian S.L.,
Tripathi Anadya P.,
Rodrigues Heidi,
Nesheiwat Dalal,
Passos Vanessa Q.,
Hu Ke
Publication year - 2014
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 - 10.1002/jcph.325
Subject(s) - pharmacokinetics , verapamil , pasireotide , medicine , pharmacology , concomitant , calcium , growth hormone , hormone , acromegaly
We evaluated the drug‐drug interaction between pasireotide SC and verapamil, a known P‐glycoprotein inhibitor. Subjects received pasireotide SC (single dose, 600 μg) on day 1, and samples for pharmacokinetics evaluation were collected from days 1 to 8. Subjects received an oral dose of verapamil 240 mg/d for 10 days (days 15–24). On day 18, subjects also received pasireotide SC 600 μg. Pharmacokinetic sampling for pasireotide SC and verapamil was done during days 18 to 25 and days 15 to 21, respectively. Safety evaluations were performed throughout the study period, including a 30‐day post‐treatment follow‐up. Pharmacokinetic profiles of pasireotide SC alone and in combination with verapamil sustained‐release (SR) were superimposable with the geometric mean ratios (90% confidence interval [CI]) of 0.98 (0.91–1.06) for C max , 0.97 (0.90–1.04) for AUC last , and 0.98 (0.92–1.05) for AUC inf . Exploratory analyses showed a 17% (90% CI, 0.72–0.94) reduction in C trough and 31% (0.58–0.82) reduction in C max (8 hours post‐dose) for verapamil SR with pasireotide SC versus verapamil alone. Pasireotide SC with or without verapamil was well tolerated. In conclusion, there was no change in the rate of pasireotide absorption and elimination or extent of exposure following concomitant administration with verapamil.