Source: Registered Drug Product Database (NG) Publisher: Krishat Pharma Industries Limited, KM 15, Lagos-Ibadan Expressway, Ibadan, Oyo State, NIGERIA., Email: info@krishatpharma.com, Company contacts details: operations@krishatpharma.com
Loperamide binds to the opiate receptor in the gut wall, reducing propulsive peristalsis, increasing intestinal transit time and enhancing resorption of water and electrolytes. Loperamide increases the tone of the anal sphincter, which helps reduce faecal incontinence and urgency.
In a double blind randomised clinical trial in 56 patients with acute diarrhoea receiving loperamide, onset of anti-diarrhoeal action was observed within one hour following a single 4 mg dose. Clinical comparisons with other anti-diarrhoeal drugs confirmed this exceptionally rapid onset of action of loperamide.
In man, Loperamide hydrochloride prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Clinical studies have indicated that the apparent elimination half-life of Loperamide hydrochloride in man is 10.8 hours with a range of 9.1 to 14.4 hours. Plasma levels of unchanged drug remain below 2 nanograms per mL after the intake of a 2 mg Loperamide hydrochloride. Plasma levels are highest approximately five hours after administration of the tablet and 2.5 hours after the liquid. The peak plasma levels of Loperamide were similar for both formulations. Elimination of Loperamide mainly occurs by oxidative N-demethylation. Cytochrome P450 (CYP450) isozymes, CYP2C8and CYP3A4, are thought to play an important role in Loperamide N-demethylation process since quercetin (CYP2C8 inhibitor) and ketoconazole (CYP3A4 inhibitor) significantly inhibited the N-demethylation process in vitro by 40% and 90%, respectively. In addition, CYP2B6 and CYP2D6 appear to play a minor role in Loperamide N-demethylation. Excretion of the unchanged Loperamide and its metabolites mainly occurs through the feces. In those patients in whom biochemical and hematological parameters were monitored during clinical trials, no trends toward abnormality during Loperamide hydrochloride therapy were noted.
Acute and chronic studies on loperamide showed no specific toxicity. Results of in vivo and in vitro studies carried out indicated that loperamide is not genotoxic. In reproduction studies, very high doses (40 mg/kg/day – 240 times the maximum human use level) loperamide impaired fertility and foetal survival in association with maternal toxicity in rats. Lower doses had no effects on maternal or foetal health and did not affect peri- and post-natal development.
Non-clinical in vitro and in vivo evaluation of Loperamide indicates no significant cardiac electrophysiological effects within its therapeutically relevant concentration range and at significant multiples of this range (up to 47-fold). However, at extremely high concentrations associated with overdoses (see section 4.4), Loperamide has cardiac electrophysiological actions consisting of inhibition of potassium (hERG) and sodium currents, and arrhythmias.
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