Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: Glaxo Wellcome UK Ltd, T/A GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex, UB11 1BT
Pharmacotherapeutic group: H2-receptor antagonists
ATC code: A02BA02
Ranitidine is a specific, rapidly acting histamine H2-antagonist. It inhibits basal and stimulated secretion of gastric acid, reducing both the volume and the acid and pepsin content of the secretion.
The clinical data available mentions the use of ranitidine in children to prevent stress ulcers. No direct evidence for prevention of stress ulcers is available. Treatment for these patients is based on the observation that pH is above 4 after administration of ranitidine. The value of this surrogate parameter in children with stress ulcers remains to be established.
Absorption of ranitidine after intramuscular injection is rapid and peak plasma concentrations are usually achieved within 15 minutes of administration.
Ranitidine is not extensively bound to plasma proteins (15%), but exhibits a large volume of distribution ranging from 96 to 142 L.
Ranitidine is not extensively metabolised. The fraction of the dose recovered as metabolites is similar after both oral and i.v. dosing; and includes 6% of the dose in urine as the N-oxide, 2& as the S-oxide, 2% as desmethylranitidine and 1 to 2% as the furoic acid analogue.
Plasma concentrations decline bi-exponentially, with a terminal half-life of 2-3 hours. The major route of elimination is renal. After IV administration of 150 mg 3H-ranitidine, 98% of the dose was recovered, including 5% in faeces and 93% in urine, of which 70% was unchanged parent drug. After oral administration of 150 mg 3H-ranitidine, 96% of the dose was recovered, 26% in faeces and 70% in urine of which 35% was unchanged parent drug. Less than 3% of the dose is excreted in bile. Renal clearance is approximately 500 mL/min, which exceeds glomerular filtration indicating net renal tubular secretion.
Limited pharmacokinetic data show that there were no significant differences in half-life (range for children 3 years and above: 1.7-2.2 h) and plasma clearance (range for children 3 years and above: 9-22 ml/min/kg) between children and healthy adults receiving intravenous ranitidine when correction is made for body weight. Pharmacokinetic data in infants is extremely limited but appears to be in line with that for older children.
In patients over 50 years of age, half-life is prolonged (3-4 h) and clearance is reduced, consistent with the age-related decline of renal function. However, systemic exposure and accumulation are 50% higher. This difference exceeds the effect of declining renal function, and indicates increased bioavailability in older patients.
Limited pharmacokinetic data from term babies undergoing treatment with Extracorporeal Membrane Oxygenation (EMCO) suggests that plasma clearance following iv administration may be reduced (1.5-8.2 ml/min/kg) and the half-life increased in the new-born. Clearance of ranitidine appeared to be related to the estimated glomerular filtration rate in the neonates.
Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction and development.
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