The disposition and elimination of meperidine were compared in drug and alcohol-free, age-matched groups of 8 normal volunteers and 10 patients with cirrhosis of the liver, while controlling the urinary pH at 7.0 or more. After a single rapid intravenous injection, 0.8 mg/kg, plasma meperidine concentration declined biexponentially with the fast (α) and slow (β) phases having half-lives in the normal group of 0.19 hr and 3.2 hr (mean values), respectively. In the cirrhotics T 1 2α was not changed but T 1 2β increased to 7.0 hr (p < 0.001), and this was associated with a reduction in the total plasma meperidine clearance from 1,316 ml/min to 664 ml/min (p < 0.002). Analysis of the data by a two-compartment open model indicated that meperidine was extensively distributed; initial distribution volume (V1), 1.54 l/kg and volume o f distribution at steady-state (Vdss), 4.17 l/kg in control subjects. Similar volumes of distribution were noted in cirrhotic patients. The overall first-order elimination rate constant, k13, decreased from 0.672 hr-1 in the normal subjects to 0.242 hr-1 in the cirrhotics (p < 0.001). The plasma binding (64.3%) and the blood/plasma concentration ratio (0.683) o f meperidine in control subjects were not altered in cirrhosis. There were no significant correlations found between T 1 2β or plasma clearance in the cirrhotics and the usual biochemical hepatic function tests. The metabolite, normeperidine, was not detected in the plasma o f either group. It is concluded that the elimination of meperidine is prolonged in cirrhosis, probably due to impairment o f drug-metabolizing activity in the liver. Accordingly, caution should be exercised when this drug is administered, particularly for long periods, to patients with cirrhosis.
ASJC Scopus subject areas
- Pharmacology (medical)