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Empirin Codeine

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Empirin Codeine

CLINICAL PHARMACOLOGY

Aspirin

The analgesic, anti-inflammatory and antipyretic effects of aspirin are believed to result from inhibition of the synthesis of certain prostaglandins. Aspirin interferes with clotting mechanisms primarily by diminishing platelet aggregation; at high doses prothrombin synthesis can be inhibited.

Aspirin in solution is rapidly absorbed from the stomach and from the upper small intestine. About 50 percent of an oral dose is absorbed in 30 minutes and peak plasma concentrations are reached in about 40 minutes. Higher than normal stomach pH or the presence of food slightly delays absorption.

Once absorbed, aspirin is mainly hydrolyzed to salicylic acid and distributed to all body tissues and fluids, including fetal tissue, breast milk and the central nervous system (CNS). Highest concentrations are found in plasma, liver, renal cortex, heart and lung. From 50 to 80 percent of the salicylic acid and its metabolites in plasma are loosely bound to proteins. The plasma half- life of total salicylate is about 3.0 hours, with a 650 mg dose. Higher doses of aspirin cause increases in plasma salicylate half- life. Metabolism occurs primarily in the hepatocytes. The major metabolites are salicyluric acid (75%), the phenolic and acyl glucuronides of salicylate (15%), and gentisic and gentisuric acid (< 1%).

Almost all of a therapeutic dose of aspirin is excreted through the kidneys, either as sailcylic acid or the above mentioned metabolic products. Renal clearance of salicylates is greatly augmented by an alkaline urine, as is produced by concurrent administration of sodium bicarbonate or potassium citrate.

Toxic salicylate blood levels are usually above 30 mg/ 100 mL. The single lethal dose of aspirin in normal adults is approximately 25- 30 g, but patients have recovered from much larger doses with appropriate treatment.

Codeine

Codeine probably exerts its analgesic effect through actions on opiate receptors in the CNS. Codeine is readily absorbed from the gastrointestinal tract, and a therapeutic dose reaches peak analgesic effectiveness in about 2 hours and persists for 4 to 6 hours. Oral codeine (60 mg) given to healthy males has been shown to achieve peak blood levels of 0.016 mg/100 mL at approximately one hour post-dose. The codeine plasma half-life for a 60 mg oral dose is about 2.9 hours. Blood levels causing CNS depression begin at 0.05-0.19 mg/100 mL. The single lethal dose of codeine in adults is estimated to be approximately 0.5-1.0 g. Codeine is rapidly distributed from blood to body tissues and taken up preferentially by parenchymatous organs such as liver, spleen and kidney. It passes the blood-brain barrier and is found in fetal tissue and breast milk.

The drug is not bound by plasma proteins nor is it accumulated in body tissues. Codeine is metabolized in liver to morphine and norcodeine, each representing about 10 percent of the administered dose of codeine. About 90 percent of the dose is excreted within 24 hours, primarily through the kidneys. Urinary excretion products are free and glucuronide-conjugated codeine (about 70%), free and conjugated norcodeine (about 10%), free and conjugated morphine (about 10%), normorphine (under 4%) and hydrocodone (<1%). The remainder of the dose appears in the feces.

Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.

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