Lack of Interaction between Lansoprazole and Propranolol, a Pharmacokinetic and Safety Assessment

• Published in: Journal of clinical pharmacology 2000-03, Vol.40 (3), p.301-308
• Main Authors: Karol, Michael D., Locke, Charles S., Cavanaugh, John H
• Format: Article
• Language: English
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles; Adrenergic beta-Antagonists - adverse effects; Adrenergic beta-Antagonists - pharmacokinetics; Adrenergic beta-Antagonists - pharmacology; Adult; Anti-Ulcer Agents - adverse effects; Anti-Ulcer Agents - pharmacology; Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Cross-Over Studies; Digestive system; Double-Blind Method; Drug Interactions; Humans; Lansoprazole; Male; Medical sciences; Omeprazole - adverse effects; Omeprazole - analogs & derivatives; Omeprazole - pharmacology; Pharmacology. Drug treatments; Propranolol - adverse effects; Propranolol - pharmacokinetics; Propranolol - pharmacology; Proton Pump Inhibitors
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00912700022008856

Due to the prevalence of both gastrointestinal and cardiovascular diseases, it is likely that patients may be coprescribed gastric parietal cell proton pump inhibitors and beta‐adrenergic antagonists. Therefore, the objectives of this phase I study were to assess the potential effects of the coadministration of lansoprazole on the pharmacokinetics of propranolol and to evaluate the safety of propranolol with concomitant lansoprazole dosing. In a double‐blind fashion, 18 healthy male nonsmokers were initially randomized to receive either 60 mg oral lansoprazole, each morning for 7 days, or an identical placebo (period 1). On day 7, all subjects were concomitantly administered oral propranolol, 80 mg. After a minimum of 1 week following the last dose of either lansoprazole or placebo, subjects were crossed over to the opposite treatment for another 7 days (period 2). Subjects were again administered oral propranolol on day 7. During both treatment periods, blood samples for the determination of plasma propranolol and 4‐hydroxy‐propranolol were obtained just before the dose and at 0.5, 1, 2, 3, 4, 6, 8 12, 16, 20, and 24 hours postdose. Plasma propranolol and 4‐hydroxy‐propranolol concentrations were determined by using HPLC with fluorescence detection. The Cmax, tmax, AUCQ0‐∞, and t1/2 values for propranolol, as well as the AUC0‐∞ for 4‐hydroxy‐propranolol, were calculated and compared between the lansoprazole and placebo regimens. The mean age of the 15 subjects who successfully completed the study was 31 years (range: 24–38 years), and their average weight was 174.8 pounds (range: 145–203 pounds). There were no statistically significant differences between the lansoprazole and placebo regimens for the propranolol Cmax, tmax, AUC0‐∞, and t1/2 values. Also, there were no statistically significant differences between regimens for the 4‐OH‐propranolol AU0‐∞. Safety evaluations, which included adverse events, vital signs, clinical laboratory determinations, ECG, and physical examinations, revealed no unexpected clinically significant findings and did not suggest a drug‐drug interaction. In conclusion, lansoprazole does not significantly alter the pharmacokinetics of propranolol, suggesting that it does not interact with the CYP2D6‐ or CYP2C19‐mediated metabolism of propranolol. Modification of a propranolol dosage regimen in the presence of lansoprazole is not indicated, based on the pharmacokinetic analysis and the lack of a clinically significant alteration i