Abstract
Aim:
To investigate the influence of omeprazole on the pharmacokinetics of domperidone given as free base and maleate salt.
Methods:
An open, randomized, 2-period crossover study with a washout period of 7 d was conducted in 10 healthy Chinese, male patients. In each study period, the patients were administered a single oral dose of 10 mg domperidone as free base or maleate salt on d 1, 20 mg omeprazole twice daily on d 2 and 3, and once on d 4. A single dose of 10 mg domperidone as free base or maleate salt was taken at 4 h after administration of omeprazole on d 4. Plasma samples were collected on d 1 and 4 after the administration of domperidone, and the plasma concentrations of domperidone were determined by a sensitive liquid chromatography-tandem mass spectrometry method.
Results:
For free-base domperidone, pretreatment with omeprazole resulted in a 16% decrease in maximum concentration (Cmax), compared with administration alone (P<0.05). However, for maleate salt, with the exception of an increase in t½, no pharmacokinetic parameters were significantly changed. When the free base and maleate salt were administered alone, no differences were found in any parameters between the 2 formulations. In contrast, when they were administered in the presence of omeprazole, the Cmax of domperidone given as free base was lower (25.9%) than that given as maleate salt (P<0.05).
Conclusion:
Pretreatment of omeprazole does not affect the absorption of domperidone maleate, but leads to a moderately decreased rate of absorption of the free base.
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References
Rowland M, Tozer TN . Clinical pharmacokinetics, concepts and applications. Philadelphia, USA: Lippincott Williams & Wilkins; 1995.
Hatlebakk JG, Berstad A . Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. Clin Pharmacokinet 1996; 31: 386–406.
Huang YC, Colaizzi JL, Bierman RH, Woestenborghs R, Heykants JJ . Pharmacokinetics and dose proportionality of domperidone in healthy volunteers. J Clin Pharmacol 1986; 26: 628–32.
Barone JA . Domperidone: a peripherally acting dopamine 2-receptor antagonist. Ann Pharmacother 1999; 33: 429–40.
Jiang SP, Liang RY, Zeng ZY, Liu QL, Liang YK, Li JG . Effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease. World J Gastroenterol 2003; 9: 1123–5.
Yu HL, Chen XY, Zhong DF . Determination of domperidone in human plasma by liquid chromatography-tandem spectrometry. J Instrument Anal 2005; 24 Suppl 5: 149–50. Chinese.
Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS . Domperidone, a review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Drugs 1982; 24: 360–400.
Gan KH, Geus WP, Lamers CB, Heijerman HG . Effect of omeprazole 40 mg once daily on intraduodenal and intragastric pH in H. pylori-negative healthy subjects. Dig Dis Sci 1997; 42: 2304–9.
Cederberg C, Rohss K, Lundborg P, Olbe L . Effect of once daily intravenous and oral omeprazole on 24–hour intragastric acidity in healthy subjects. Scand J Gastroenterol 1993; 28: 179–84.
Hartmann M, Theiss U, Huber R, Luhmann R, Bliesath H, Wurst W, et al. Twenty-four-hour intragastric pH profiles and pharmacokinetics following single and repeated oral administration of the proton pump inhibitor pantoprazole in comparison to omeprazole. Aliment Pharmacol Ther 1996; 10: 359–66.
Graham DY, Opekun AR, Jogi M, Yamaoka Y, Lu H, Reddy R, et al. False negative urea breath tests with H2–receptor antagonists: interactions between Helicobacter pylori density and pH. Helicobacter 2004; 9: 17–27.
Li XQ, Andersson TB, Ahlstrom M, Weidolf L . Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004; 32: 821–7.
Simard C, Michaud V, Gibbs B, Masse R, Lessard E, Turgeon J . Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone. Xenobiotica 2004; 34: 1013–23.
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Zhang, Yf., Chen, Xy., Dai, Xj. et al. Influence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients. Acta Pharmacol Sin 28, 1243–1246 (2007). https://doi.org/10.1111/j.1745-7254.2007.00596.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00596.x