Normeperidinic acid

Meperidine is in part demethylated in the body appearing as normeperidine in the urine. It is, however, for the most part hydrolyzed and excreted as free and conjugated meperidinic acid. The normeperidine is also partially hydrolyzed to normeperidinic acid, which is partly conjugated. Only a small part of the drug is excreted in an unchanged form. In humans, meperidine is metabolized at the rate of about 17% per hour, so that a single dose exerts its analgesic effect for 3 to 4 h. In the dog, on the other hand, its rapid metabolism (70 to 90% per hour) makes it difficult to induce tolerance or addiction. 

Metabolism and Elimination of Other Opioid Agents. Meperidine is also metabolized in the liver. It is either hydrolyzed directly to meperidinic acid or N-demethylated to normeperidine and then hydrolyzed to normeperidinic acid. The acid forms are conjugated, then excreted (23). 

Asatoor et al 2 determined that in highly acidic urine the main route of removal of meperidine hydrochloride from the body is by excretion of meperidine and normeperidine. If the urine is alkaline, excretion of the hydrolysis products meperidinic and normeperidinic acids, both as free acids and as conjugates, is the more important means of elimination. 

In humans, meperidine is hydrolyzed to meperidinic acid, which, in turn, is partially conjugated. Meperidine also is N-demethylated to normeperidine, which then may be hydrolyzed to normeperidinic acid and subsequently conjugated. Meperidine is metabolized chiefly in the hver, with a half-life of about 3 hours. In patients with cirrhosis, the bioavailability of meperidine is increased to as much as 80%, and the half-lives of both meperidine and normeperidine are prolonged. Approximately 60% of meperidine in plasma is protein bound. Only a small amount is excreted unchanged. 

Meperidine 50-100 mgq. 3-4 hr Hepatic 100% avoid avoid Normeperidine, an active metabolite, accumulates in ESRD and may cause seizures protein binding is reduced in ESRD 20%-25% of meperidine is excreted unchanqed in acidic urine Avoid Avoid Avoid... 

In a study by Burns et al 9 in which the plasma levels of meperidine hydrochloride were measured after intravenous injection in man, it was inferred that metabolism occurs at a rate varying from 10 to 20 per hour (17 average) in ten different subjects. No accumulation of the drug after repeated administration was found in this study and only 5 of the drug was found to be excreted unchanged in the urine. Plotnikoff et al3l determined that the biotransformation products of meperidine hydrochloride excreted in human urine are normeperidine (I), meperidinic acid (II), nor-... 

Maruyama O used a ring oven paper chromatographic method to separate meperidine and normeperidine from the free acids. 

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