Pethidine half-life

Pharmacokinetic properties Pethidine (Mather and Meffin, 1978) has a faster onset and a shorter duration of action than morphine. After oral administration about 50% of the drug is eliminated by first-pass metabolism. N-demethylation yields the active metabolite nor-pethidine, and hydrolytic cleavage the inactive metabolites pethidinic and nor-pethidinic acid. The half-life of pethidine is about 3- 6 h. Nor-pethidine has a much slower elimination with a half life of up to 20 h. 

The symptoms described here resemble the 5HT toxicity syndrome (SEDA-25,16) and suggest that pethidine can provoke this reaction when combined with SSRIs, as it can with monoamine oxidase inhibitors. The report is also a useful reminder that the active metabolite of fluoxetine, norfluoxetine, has a half-life of about 1 week and would still have been present at the time of endoscopy, even though fluoxetine had been stopped 14 days before. 

Cirrhotic patients and those with acute viral hepatitis have experienced a doubling of the half-life of pethidine and a corresponding reduction in clearance compared to healthy subjects. 

Pethidine Mean 50 40-50 3-6 0.6-27 (pH dependent, less with higher pH) No information [47] Extensive in liver via hydrolysis and N-demethylation, followed by partial conjugation. First pass metabolism of 47-61% Yes. Norpethidine which is half as potent an analgesic, but potent convulsant -causes tremor and seizures Fong half-life, up to 20 hours Cleared renally... 

The active metabolite of pethidine has a longer half life. 

Norpethidine, a metabolite of pethidine, can cause tremor and seizures. The risk increases following repeated doses, owing to accumulation of the metabolite (longer half-life than pethidine) and resulting high plasma concentrations. Although patients with cirrhosis may have impaired formation of norpethidine, they may still be at increased risk of cumulative toxicity because of the slower elimination of the metabolite and their increased sensitivity to the effects of opioids [57]. 

One small study showed that five men with hepatic cirrhosis had significantly lower pethidine clearance, greater bioavailability and longer half-life than six healthy subjects. The average half-life was increased from 5.2 hours to 11.4 hours in the cirrhotic group [57]. 

Norpethidine, a metabolite of pethidine, which has a longer half-life, may accumulate in cirrhosis, can cause tremor, and also has convulsant properties. 

Half-life. Plasma half-life, pethidine 3 to 10 hours (mean 5), increased in neonates and in renal impairment norpethidine about 18 hours. 

Pethidine (meperidine) is about one-tenth as potent as morphine in terms of analgesia. It is metabolized in the liver by hydrolysis and conjugation, either directly or via N-demethylation to norpethidine. Norpethidine (norme-peridine) is significantly less analgesic, with a longer half-life (15-20 hours). 

It is known that phenytoin increases the metabolism of pethidine with increased production of norpethidine, the metabolic product of pethidine that is believed to be responsible for its neurotoxicity (seizures, myoclonus, tremors etc). A study in healthy subjects found that phenytoin 300 mg daily for 9 days decreased the elimination half-life of pethidine (100 mg orally and 50 mg intravenously) from 6.4 to 4.3 hours, and the systemic clearance increased by 27%. This seems to be the only report of an adverse interaction between phenytoin and pethidine so its general importance is uncertain. Since the study cited found that pethidine given orally produced more of the toxic metabolite (norpethidine) than when given intravenously, it may be preferable to give pethidine intravenously in patients taking phenytoin, or use an alternative opioid. 

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