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Pharmacokinetics of an Oral Drug (Acetaminophen) Administered at Various Times in Relation to Subcutaneous Injection of Exenatide (Exendin‐4) in Healthy Subjects
Author(s) -
Blase Erich,
Taylor Kristin,
Gao Hongye,
Wintle Matthew,
Fineman Mark
Publication year - 2005
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 - 10.1177/0091270004274432
Subject(s) - exenatide , placebo , acetaminophen , medicine , pharmacokinetics , crossover study , pharmacology , analgesic , anesthesia , nausea , adverse effect , vomiting , gastroenterology , type 2 diabetes , diabetes mellitus , endocrinology , alternative medicine , pathology
Exenatide is an incretin mimetic with potential glucoregulatory activity in type 2 diabetes. This randomized, single‐blind, placebo‐controlled 6‐way crossover study assessed exenatide's effect on acetaminophen pharmacokinetics. Of 40 randomized healthy subjects, 39 completed the study. On the placebo day, acetaminophen (1000 mg) was ingested and placebo injected subcutaneously at 0 hours. On exenatide days, acetaminophen was ingested at −1, 0, +1, +2, and +4 hours, relative to the 10 μg exenatide injected subcutaneously at 0 hours. With exenatide injection, mean plasma acetaminophen AUC 0–12 h values were reduced by 11% to 24% (vs placebo). Peak plasma acetaminophen concentrations were similar for the −1‐hour and placebo groups and reduced by 37% to 56% at other times. The most frequent adverse events were generally mild to moderate nausea and vomiting. Exenatide treatment concurrent with or preceding acetaminophen ingestion slowed acetaminophen absorption but had minimal effect on the extent of absorption.