Abstract
The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice for treatment of these diseases. However, its efficacy can be improved by combining with spasmolytic and/or visceral analgesic such as hyoscine butylbromide. Since hyoscine butylbromide is barely absorbed and exerts some local effects at gastrointestinal tract which may modify the absorption of lansoprazole, it is important to establish if there is a pharmacokinetic interaction after the oral concomitant administration of both drugs. For this objective, twenty-five subjects received under a crossover design an oral administration of lansoprazole (15 mg) plus placebo or a fixed-dose combination with hyoscine butiylbromide (15 mg + 10 mg, respectively). Plasma samples were obtained at different times during 10 hours. Lansoprazole plasma concentrations were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Fixed-dose combination was well tolerated. Lansoprazole pharmacokinetic parameters were: Cmax 621.81 ± 212.79 and 450.38 ± 192.14 ng/mL; AUC0-t 1941.36 ± 845.57 and 1454.66 ± 757.28 ng·h/mL; tmax 2.83 ± 0.99 and 3.40 ± 1.82h; t1/2 1.35 ± 0.39 and 1.45 ± 0.51 h, for alone and combined fixed-dose formulation, respectively. Pharmacokinetic parameters were compared by analysis of variance and ratios of AUC0-t, Cmax and 90% confidence intervals obtained. Since confidence intervals exceed the 80% - 125% limits for these parameters, we conclude that there is a significantly pharmacokinetic interaction of lansoprazole when it is administered concomitantly with hyoscine butylbromide.
Highlights
The acid-related disorders (ARD) include gastroesophageal reflux disease, peptic ulcer disease and stress-related erosive syndrome [1]
Since the possible influence of hyoscine butylbromide on lansoprazole pharmacokinetics has not yet been determined, in this study we evaluate the possible pharmacokinetic interaction between these drugs when are administered concomitantly in a fixed-dose combination in comparison with an equal formulation of lansoprazole plus placebo
Lansoprazole oral pharmacokinetics was characterized in all subjects enrolled and no important adverse events were observed
Summary
The acid-related disorders (ARD) include gastroesophageal reflux disease, peptic ulcer disease and stress-related erosive syndrome [1]. Lansoprazole is metabolized in the liver to 5-hydroxylansoprazole and lansoprazole sulfone by CYP2C9 and CYP3A4, respectively [8] It has a short elimination half-life (t1/2) ≈ 1 hour, this value is not related with the duration of gastric acid suppression [3] [9] [10] which is a pharmacological aspect that promotes the use of lansoprazole in the therapeutic field. Under some situations patients have a poor therapeutic response for ARD symptoms with the use of a PPI like lansoprazol For these situations, the medical treatment can be improved trough the concomitant administration of drugs with therapeutic effects focused to reduce transient lower esophageal sphincter relaxation rate or decrease esophageal pain perception by using visceral analgesics [11]. Since the possible influence of hyoscine butylbromide on lansoprazole pharmacokinetics has not yet been determined, in this study we evaluate the possible pharmacokinetic interaction between these drugs when are administered concomitantly in a fixed-dose combination in comparison with an equal formulation of lansoprazole plus placebo
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