Effect of exenatide on lisinopril pharmacodynamics in patients treated for hypertension

Abstract

Background/Aims Exenatide's antihyperglycemic actions under investigation include slowing gastric emptying, which may affect absorption of co-administered oral drugs. This study evaluated that potential effect with lisinopril, an ACE inhibitor. Methods This double-blind, placebo (PBO)-controlled, crossover study had 19 subjects (11M/8F; 59±6 y; 81.0±14.8 kg; mean±SD) without diabetes, treated with lisinopril for hypertension (5 to 20 mg, 5 min post breakfast, ≥30 d), randomized to subcutaneous doses of exenatide (10 μg) or PBO, 15 min before breakfast and dinner on 1d separated by ≥2-d washout period. Ambulatory blood pressure (BP) and lisinopril pharmacokinetics were measured for 24-h post dose. The predefined 95% CI limit for no clinically relevant difference in diastolic BP was 8 mmHg. Results 24-h diastolic and systolic BP means were not significantly different between exenatide and PBO administered with lisinopril. LSmean (95% CI) for 24-h differences between treatments were 1.38 mmHg (−1.41, 4.17) for diastolic and 1.38 mmHg (−1.95, 4.71) for systolic BP. Exenatide did not alter steady-state lisinopril Cmax and AUCτ but increased lisinopril Tmax by 2h. Mild-to-moderate gastrointestinal disorders were more frequent with exenatide, and no hypoglycemia or hypotension occurred. Conclusions Exenatide was generally well tolerated and did not significantly affect the BP response to lisinopril suggesting exenatide may be co-administered without adjusting lisinopril dosage. Clinical Pharmacology & Therapeutics (2005) 77, P14–P14; doi: 10.1016/j.clpt.2004.11.056