The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam
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The effects of the benzamide cisapride (C) (8 mg) i.v. have been compared to placebo (P) in a double blind randomised study. The effects on gastric emptying, the absorption and effects of oral diazepam, and BP and pulse were observed.
Cisapride increased the rate of gastric emptying of 500 ml liquid containing diazepam 10 mg (t1/2 C: 7.4 min, P: 14.9 min). The initial rate of absorption of diazepam contained in the drink was increased by C (AUC 0–1 h C: 328 µg h 1−1, P: 253 µg h 1−1, but there was no change in overall bioavailability. This change in diazepam kinetics was associated with a significantly greater impairment in reaction time in the first 45 min after drinking but not in self rated sedation. Cisapride produced a significant tachycardia (e.g. after 10 min C: 82 beats/min, P: 69 beats/min) which probably reflects a peripheral vasodilator action. Cisapride may therefore alter the pharmacokinetics and dynamics of concurrently administered drugs.
Key wordscisapride diazepam absorption drug interaction pharmacokinetics pharmacodynamics
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- 1.Reyntjens A, Verlinden M, Schuurkes J, Van Neuten J, Janssen PAJ (1984) New approach to gastrointestinal motor dysfunction: Non-dopaminergic non-cholinergic stimulation with cisapride. Curr Ther Res 36: 1029–1037Google Scholar
- 2.Reyntjens A, Verlinden M, DeCoster R, Janisch HD, Smout A, De Cree J, Leempoels J, Verhagen H (1984) Clinical pharmacological evidence for cisaprides lack of antidopaminergic or direct cholinergic properties. Curr Ther Res 36: 1045–1052Google Scholar
- 3.Bateman DN, Whittingham TA (1982) Measurement of gastric emptying by real-time ultrasound. Gut 23: 524–527Google Scholar
- 4.Rutherford DM (1977) Rapid micro method for the measurement of diazepam and desmethyl diazepam in blood plasma by gas liquid chromatography. J Chromatogr 137: 439–448Google Scholar
- 5.Brown DR, Mannor JE (1978) ESTRIP a Basic computer program for obtaining initial polyexponential parameter estimates. J Pharm Science 67: 1687–1691Google Scholar
- 6.Rawlins MD, Bateman DN (1984) The contribution of absorption to variation in response to drugs. In: Prescott LF, Nimmo WS (eds) Rate control in drug therapy. Churchill Livingstone, Edinburgh, p 11–12Google Scholar
- 7.Prescott LF (1974) Gastric emptying and drug absorption. Br J Clin Pharmacol 1: 189–190Google Scholar
- 8.Bateman DN, Kahn C, Mashitor K, Davies DS (1978) Pharmacokinetics and concentration effect studies with intravenous metoclopramide. Br J Clin Pharmacol 6: 401–407Google Scholar
- 9.Garnham JC, Raymond K, Shottoon E, Turner P (1975) The effect of buffered aspirin on plasma indomethain. Eur J Clin Pharmacol 8: 107–113Google Scholar
- 10.Pottage A, Campbell RFW, Achuff SC, Murray A, Julian DG (1978) The absorption of oral mexilitine in coronary care patients. Eur J Clin Pharmacol 13: 393–399Google Scholar
- 11.Nimmo WS (1981) Gastric emptying and drug absorption. In: Prescott LF, Nimmo WS (eds) Drug absorption. Aldis Press, p 11–18Google Scholar
- 12.Finch JE, Kendall MJ, Mitchard M (1974) An assessment of gastric emptying by breathalyser. Br J Clin Pharmacol 1: 233–236Google Scholar
- 13.Heading RC, Nimmo J, Prescott LF, Totnill P (1973) The dependence of paracetamol absorption on the rate of gastric emptying. Br J Pharmacol 47: 405–412Google Scholar
- 14.Greenblatt DJ, Abernethy DR, Morse DS, Harmatz JS, Shador RI (1984) Clinical importance of the interaction of diazepam and cimetidine. N Engl J Med 310: 1639–1643Google Scholar
- 15.Bateman DN (1985) Studies on the pharmacological control of gastric emptying in man. Br J Clin Pharmacol 20: 339–344Google Scholar
- 16.Bateman DN, Gooptu D, Whittingham TA (1982) The effects of domperidone on gastric emptying of liquid in man. Br J Clin Pharmacol 13: 675–678Google Scholar