RANITIDINE HCL

Chemistry - An H2 receptor antagonist, ranitidine HCl occurs as a white to pale-yellow granularsubstance with a bitter taste and a sulfur-like odor. The drug has pKas of 8.2 and 2.7. One gram isapproximately soluble in 1.5 ml of water or 6 ml of alcohol. The commercially available injectionhas a pH of 6.7-7.3.

Storage, Stability, Compatibility

Ranitidine tablets should be stored in tight, light-resistantcontainers at room temperature. The injectable product should be stored protected from light and ata temperature less than 30°C. A slight darkening of the injectable solution does not affect thepotency of the drug.
Ranitidine injection is reportedly stable for up to 48 hours when mixed with the commonly used IV solutions (including 5% sodium bicarbonate).

Pharmacology - RANITIDINE HCL

At the H2 receptors of the parietal cells, ranitidine competitively inhibits histamine, thereby reducing gastric acid output both during basal conditions and when stimulated by food, amino acids, pentagastrin, histamine or insulin. Ranitidine is between 3-13 times more potent(on a molar basis) as cimetidine.
Ranitidine can cause gastric emptying times to be delayed, but the clinical significance of thiseffect is not known. Lower esophageal sphincter pressures may be increased by ranitidine. Bydecreasing the amount of gastric juice produced, ranitidine also decreases the amount of pepsinsecreted.
Ranitidine, unlike cimetidine, does not appear to have any appreciable effect on serum prolactinlevels, although it may inhibit the release of vasopressin.
Uses, Indications - In veterinary medicine, ranitidine has been used for the treatment and/or prophylaxis of gastric, abomasal and duodenal ulcers, uremic gastritis, stress-related or drug-inducederosive gastritis, esophagitis, duodenal gastric reflux and esophageal reflux. It has also been employed to treat hypersecretory conditions associated with gastrinomas and systemic mastocytosis.

Pharmacokinetics - RANITIDINE HCL

Pharmacokinetic data for veterinary species is limited for this product. Indogs, the oral bioavailability is approximately 81%, serum half-life is 2.2 hours and volume ofdistribution 2.6 L/kg.
In humans, ranitidine is absorbed rapidly after oral administration, but undergoes extensive first-pass metabolism with a net systemic bioavailability of approximately 50%. Peak levels occur atabout 2-3 hours after oral dosing. Food does not appreciably alter the extent of absorption or thepeak serum levels attained.
Ranitidine is distributed widely throughout the body and is only 10-19% bound to plasma proteins. Ranitidine is distributed into human milk at levels of 25-100% of those found in the plasma.
Ranitidine is both excreted in the urine by the kidneys (via glomerular filtration and tubular secretion) and metabolized in the liver to inactive metabolites; accumulation of the drug can occur inpatients with renal insufficiency. The serum half-life of ranitidine in humans averages from 2-3hours. The duration of action at usual doses is from 8-12 hours.
Contraindications/Precautions - Ranitidine is contraindicated in patients who are hypersensitiveto it. It should be used cautiously and possibly at reduced dosage in patients with diminished renalfunction. Ranitidine has caused increased serum ALT levels in humans receiving high, IV doses forlonger than 5 days. The manufacturer recommends that in high dose, chronic therapy that serum
ALT values be considered for monitoring.

Adverse Effects, Warnings

Adverse effects appear to be very rare in animals at the dosagesgenerally used. Potential adverse effects (documented in humans) that might be seen include mentalconfusion and headache. Rarely, agranulocytosis may develop and if given rapidly IV, transientcardiac arrhythmias may be seen. Pain at the injection site may be noted after IM administration.
Overdosage - Clinical experience with ranitidine overdosage is limited. In laboratory animals, veryhigh dosages (225 mg/kg/day) have been associated with muscular tremors, vomiting and rapidrespirations. Single doses of 1 gram/kg in rodents did not cause death.
Treatment of overdoses in animals should be handled using standard protocols for oral ingestionsof drugs; symptoms may be treated symptomatically and supportively if necessary. Hemodialysisand peritoneal dialysis have been noted to remove ranitidine from the body.

Drug Interactions

Unlike cimetidine, ranitidine appears to only have minimal effects on thehepatic metabolism of drugs and is unlikely to cause clinically relevant drug interactions via thismechanism.
Propantheline Bromide delays the absorption, but increases the peak serum level of ranitidine.
The relative bioavailability of ranitidine may be increased by 23% when propantheline is administered concomitantly with ranitidine.
Antacids may decrease the absorption of ranitidine; give at separate times (2 hours apart) if usedconcurrently.
Ranitidine may decrease the renal clearance of procainamide, but the clinical relevance of thisinteraction is unclear at this time.
The manufacturer states that ranitidine may alter the bioavailability of certain drugs through pH-dependent effects, changes in volume of distribution or an unknown effect. Further information ispending.
Drug/Laboratory Interactions - Ranitidine may cause a false-positive urine protein readingwhen using Multistix®. The sulfosalicylic acid reagent is recommended for determining urineprotein when the patient is concomitantly receiving ranitidine.