The disposition and elimination of meperidine (Demerol) were compared in drug and alcohol-free, age-matched groups of 15 normal volunteers and 14 patients with acute viral hepatitis, while controlling the urinary pH at 7.0 or greater. In the controls, the plasma half-life (t1/2(β)) for meperidine was 3.37 ± 0.82 hr (mean ± SD), while in hepatitis patients it was significantly prolonged to 6.99 ± 2.74 hr (P < 0.001). This increase in meperidine t1/2(β) was fully accounted for by a comparable decrease in meperidine plasma clearance, from control values of 1261 ± 527 ml per min to 649 ± 228 ml per min (P < 0.002). There was no significant difference between the two groups in the volume of distribution for meperidine [5.94 ± 2.65 liters per kg for normal versus 5.56 ± 1.80 liters per kg for hepatitis patients (P < 0.05)]. Likewise, the plasma protein binding for meperidine was comparable in both groups [58.3 ± 8.7 in normal versus 56.0 ± 11.8% in hepatitis subjects (P = 0.59)]. In 5 patients with viral hepatitis studied during their acute illness and then after recovery, the t1/2(β) fell from 8.24 ± 3.71 to 3.25 ± 0.80 hr, and meperidine plasma clearance rose from 488 ± 132 to 1200 ± 555 ml per min (P < 0.05). There was no statistically significant correlation of meperidine t1/2(β) or clearance with conventional liver function tests. It is conclude that the elimination of meperidine is significantly impaired in acute viral hepatitis and that caution should be exercised when this drug is administered, particularly for a prolonged time, to such patients.
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