Cisapride

Cispride has been reported to increase the rate of absorption of /alcohol or benzodiazepines/.

Concurrent use /with anticholinergics or other medications with anticholinergic activity/ may antagonize the effects of cisapride on gastrointestinal motility.

Cisapride accelerates the absorption of cimetidine and rantidine.

Concurrent use of itraconazole, ketoconazole, or intravenous miconazole with cisapride is contraindicated; concurrent use may result in elevated plasma concentrations of cisapride through inhibition of the cytochrome p450 metabolic pathways by these antifungals; this has led to ventricular arrhythmias, including torsades des pointes, in patients taking cisapride and ketoconazole.

For more Interactions (Complete) data for CISAPRIDE (8 total), please visit the HSDB record page.

Cisapride acts through the stimulation of the serotonin 5-HT₄ receptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Cisapride

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

No tumorigenicity was demonstrated in rats receiving up to 80 mg of cisapride/kg of body weight (mg/kg) (50 times the maximum recommended human dose for a 50 kg person) a day for 25 months or in mice receiving up to 80 mg/kg ( 50 times the maximum recommended human dose) of cisapride a day for 19 months.

No mutagenicity was demonstrated in the following in vitro and in vivo models: Ames' test, ... sex-linked recessive lethal test in Drosophila melanogaster, dominant lethal test in male and female mice germ cells and micronucleus test in rats.

At oral doses of up to 160 mg/kg a day (100 times the maximum recommended human dose), cisapride was found to have no effect on fertility in male rats. In female rats at oral doses of 40 mg/kg a day and higher, cisapride prolonged the breeding interval required for impregnation. These effects were also observed at maturity in the female offspring of female rats treated with oral doses of cisapride at 10 mg/kg a day or higher. At dose of 160 mg/kg a day, cisapride exerted contragestational/pregnancy disrupting effects in female rats.

Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief.

Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.

Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%.

The placental transfer of cisapride, a new prokinetic agent, was studied in a sheep model. The pharmacokinetics of cisapride were studied in the lamb, the pregnant ewe, and the fetus by obtaining blood samples from chronically implanted arterial catheters. Comparable pharmacokinetic parameters were found in the lamb and the adult sheep: half-life, 1.39-1.83 hr; total plasma clearance, 1998-2160 ml/kg/hr; AUC, 92.6-100.1 ng.hr/ml. Cisapride plasma concentrations after continuous infusion were predicted correctly based on the parameters obtained after IV bolus. There was a materno-fetal transfer of cisapride following a single IV bolus administered to the mother. Cisapride crossed the placenta within 5 min and equilibrated with maternal plasma within 20 to 30 min after dosing. The average fetal-to-maternal plasma concentration ratio was 0.71. The amniotic fluid also contained measurable amounts of cisapride. The protein binding of cisapride in maternal and fetal plasma is 89.0% and 88.4%, respectively; the free fraction is 4 times larger than in humans. Cisapride crosses the ovine placental barrier. The sheep placenta is less permeable than the human placenta, but the higher free fraction of cisapride facilitates placental transfer.