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Pharmacokinetics, Safety, and Tolerability of Phentermine in Healthy Participants Receiving Taranabant, a Novel Cannabinoid‐1 Receptor (CB1R) Inverse Agonist
Author(s) -
Addy Carol,
Jumes Patricia,
Rosko Kimberly,
Li Susie,
Li Hankun,
Maes Andrea,
JohnsonLevonas Amy O.,
Chodakewitz Jeffrey,
Stoch S. Aubrey,
Wagner John A.
Publication year - 2009
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 - 10.1177/0091270009341651
Subject(s) - phentermine , tolerability , pharmacokinetics , medicine , placebo , pharmacology , blood pressure , heart rate , crossover study , anesthesia , adverse effect , weight loss , alternative medicine , pathology , obesity
This study assessed the potential pharmacokinetic interaction and safety/tolerability of taranabant and phentermine coadministration. This was a randomized, double‐blind, 3‐panel, fixed‐sequence study in healthy participants. Panels A, B, and C evaluated the safety/tolerability of phentermine 15 mg coadministered with taranabant 0.5, 1, and 2 mg for 7 days (panel A) and 28 days (panels B and C). In panels A and C, phentermine 15 mg was administered both with (7 days, panel A; 28 days, panel C) and without (7 days) taranabant 0.5 mg or 2 mg to evaluate pharmacokinetics. The primary endpoint was phentermine AUC 0–24 h in panels A and C. Secondary endpoints were changes from baseline in blood pressure and heart rate for all panels. The geometric mean ratios and 90% confidence intervals for phentermine AUC 0–24 h in the presence/absence of taranabant 0.5 mg and 2 mg were 1.08 (0.99, 1.17) and 1.04 (0.98, 1.10), respectively. No significant differences in blood pressure and heart rate were observed with any treatment versus placebo. Coadministration of taranabant 0.5 mg, 1 mg, and 2 mg with phentermine was well tolerated with no pharmacokinetic interaction and did not result in meaningful changes in blood pressure or heart rate versus placebo.