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The effect of cirrhosis on the disposition and elimination of meperidine in man

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 (ß) phases having half‐lives in the normal group of 0.19 hr and 3.2 hr (mean values), respectively. In the cirrhotics T½α was not changed but T½ß 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)2 1.54 lIkg and volume of distribution at steady‐state (Vdss), 4.17 lIkg 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 hrs in the cirrhotics (p < 0.001). The plasma binding (64.3%) and the blood/plasma concentration ratio (0.683) of meperidine in control subjects were not altered in cirrhosis. There were no Significant correlations found between T½ß or plasma clearance in the cirrhotics and the usual biochemical hepatic function tests. The metabolite, normeperidine, was not detected in the plasma of either group. It is concluded that the elimination of meperidine is prolonged in cirrhosis, probably due to impairment of drug‐metaboliZing activity in the liver. Accordingly, caution should be exercised when this drug is administered, particularly for long periods, to patients with cirrhosis.