Pharmacokinetics of low-dose intravenous pethidine in patients with renal dysfunction

The kinetics and elimination of pethidine (meperidine) after intravenous administration (150 micrograms/kg) to ten healthy volunteer subjects were compared with those obtained from 18 patients who suffered from varying degrees of renal dysfunction. In both groups of subjects, pethidine was eliminated triexponentially from plasma. However, plasma concentrations in the patients (who were subdivided into patients with severe dysfunction, moderate dysfunction, and mild dysfunction) were consistently higher. The mean +/- SEM elimination half-life (t1/2) of pethidine was significantly longer in the three groups of renal patients: 7.9 +/- 1.1, 20.2 +/- 13.6, 16.6 +/- 5.4, and 14.3 +/- 3.1 hr, respectively, for healthy volunteers, patients with severe, moderate, and mild dysfunction; their mean +/- SEM creatinine clearances were 97.3 +/- 7.5, less than 9.5, 30.0 (3.7), and 63.3 +/- 8.5 mL/min respectively. The mean plasma clearance of the drug was higher in healthy subjects (342.7 +/- 62.5 mL/min) than various groups of renal patients (99.9 +/- 11.6, 120.9 +/- 45.8, and 123.8 +/- 34.1, respectively, for patients with severe, moderate, and mild dysfunction). Impairment of renal function also reduced total plasma protein binding: 58.2 +/- 5.0% in healthy subjects and 31.8 +/- 3.9%, 44.5 +/- 5.0%, and 42.5 +/- 5.6%, respectively, for the three renal patient groups. The percentage of pethidine recovered in the urine was significantly lower in the severe dysfunction group while norpethidine recovery was significantly lower in all three groups of renal patients.(ABSTRACT TRUNCATED AT 250 WORDS)