PubMed · 11665483
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M Lindberg. 2001-10-08. [Irritable colon].. https://pubmed.ncbi.nlm.nih.gov/11665483/
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OBJECTIVES: We conducted a population pharmacokinetic analysis of cisapride in neonates to study whether metabolic immaturity in this population may lead to increased concentrations. METHODS: Cisapride was administered orally in 91 neonates at the dose of 0.2 mg/kg four times a day. Plasma concentrations were measured using a validated HPLC method. A one-compartment model with first-order absorption was fitted to the data using NONMEM software. RESULTS: One to seven plasma samples were obtained from neonates aged 7-123 days. Cisapride concentrations ranged from 5.5 ng/mL to 172 ng/mL and were not higher than those reported in adults. The absorption constant rate was fixed to 2.5 h-1. Clearance (CL/F) and volume of distribution (V/F) both significantly correlated to weight (WT), but addition of this covariate in V/F did not improve the objective function after it was added in the CL/F covariate model. Prematurity, postnatal age, or coadministered drugs did not affect cisapride clearance. Final population pharmacokinetic parameters (interindividual variability) were: V/F=17,200 mL (90.4%) and CL/F=3.91 x WT(3/4) mL/h (36.3%). CONCLUSIONS: Our finding that cisapride clearance is primarily influenced by weight is in agreement with current recommendations of weight-adjusted doses. This study indicates that no clinically relevant maturational changes in cisapride clearance have to be considered during the first quadrimester of life.
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AIM: To investigate the effect of cisapride, a selective 5-hydroxytryptamine-4 receptor agonist, on the frequency of nocturnal transient lower oesophageal sphincter relaxations and oesophageal acid exposure in patients with gastro-oesophageal reflux disease. METHODS: In a double-blind, placebo-controlled study, 10 patients with gastro-oesophageal reflux disease (six male and four female; mean age, 54 +/- 10.4 years) were randomly assigned to 5-day treatments with cisapride, 10 mg q.d.s., or placebo, separated by a 2-day washout period before the treatment crossover. Sleep stages, lower oesophageal sphincter tone and oesophageal pH were monitored overnight at the end of each treatment regimen. Gastric emptying was assessed before treatment. RESULTS: Cisapride decreased the frequency of transient lower oesophageal sphincter relaxations during sleep (1.2 +/- 0.2/h vs. 2.7 +/- 0.5/h with placebo; P=0.004) and oesophageal acid exposure (17.2 +/- 9.9% with placebo vs. 7.2 +/- 4.2% with cisapride; P=0.4). Cisapride increased lower oesophageal sphincter tone from 12.7 +/- 2.8 mmHg with placebo to 16.9 +/- 3.9 mmHg (P=0.03), and decreased heartburn episodes and antacid consumption. All patients had normal gastric retention data over 4 h. CONCLUSIONS: In patients with gastro-oesophageal reflux disease, cisapride significantly decreased the frequency of transient lower oesophageal sphincter relaxations during sleep and increased lower oesophageal sphincter pressure without changing gastric emptying. We hypothesize, therefore, that 5-hydroxytryptamine-4 mechanisms are important in the control of transient lower oesophageal sphincter relaxations in humans.