Lansoprazole pharmacokinetics differ in patients with oesophagitis compared to healthy volunteers M. L. BARCLAY, E. J. BEGG, R. A. ROBSON, W. A. PETERS* & J. W. KETELBEY* Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand; and *Lederle Laboratories, Baulkham Hills, Australia Accepted for publication 6 May 1999 INTRODUCTION Lansoprazole is a proton pump inhibitor that is used in the treatment of acid-related disorders of the upper gastrointestinal tract and in regimens for the eradica- tion of gastric Helicobacter pylori infection. It is a substituted benzimidazole that binds tightly to the parietal cell membrane-bound enzyme H + /K + -ATPase and suppresses the production of acid in the parietal cells. 1 The largest patient group using lansoprazole is that requiring long-term maintenance acid suppression for the treatment of re¯ux oesophagitis. However, studies of the pharmacokinetics of lansoprazole were initially performed in young healthy volunteers, who are not representative of the usual patient population in terms of age or morbidity. It is important to know whether the pharmacokinetics of a drug are different in patients as opposed to healthy volunteers in order to optimize the dose regimen. The aim of this study was to compare the pharmacokinetics of lansoprazole in patients with re¯ux oesophagitis with the pharmacoki- netics in normal healthy volunteers, after single doses and at steady-state. PATIENTS AND METHODS Patients Eight healthy volunteers and 16 patients with re¯ux oesophagitis were enrolled. Inclusion criteria for the SUMMARY Aim: To compare the pharmacokinetics of lansoprazole in patients with re¯ux oesophagitis and in healthy volunteers, after a single dose and at steady-state. Patients and methods: A 30 mg dose of lansoprazole was administered orally daily for 7 days in eight healthy male volunteers aged 21±24 years, and in 16 patients aged 29±65 years with grade 2 or 3 re¯ux oesophagitis. The pharmacokinetics were assessed over the 24 h dose interval following the ®rst dose and again after the 7th dose. Results: Within both the patient and volunteers groups, there were no signi®cant differences between day 1 and day 7 in any of the pharmacokinetic parameters including maximum concentration (C max ), area under the concentration±time curve (AUC), and terminal half- life of elimination (t  ). However, on both days 1 and 7, values were signi®cantly higher in the patients than in the healthy volunteers. On day 7, C max was 1343 ng/mL in patients compared with 765 ng/mL in healthy volunteers, AUC was 3458 ng.h/mL vs. 1350 ng.h/mL and t  was 1.62 h vs. 0.90 h. Conclusion: The differences in results for the pharmaco- kinetics re¯ect reduced lansoprazole clearance in the patient group. Other research has not found a difference in pharmacokinetics when comparing healthy volunteers with patients with acid-related disorders. The difference in lansoprazole clearance in this study may be related to a variety of factors that are different in patients compared with young normal volunteers, such as age, gender, other drugs, and reduced general well-being. Correspondence to: Dr M. L. Barclay, Department of Clinical Pharmacol- ogy, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand. Aliment Pharmacol Ther 1999; 13: 1215±1219. Ó 1999 Blackwell Science Ltd 1215