An analysis of the inter-subject variation in the metabolism of pentazocine

Abstract

Significant inter‐subject variation in the cumulative urinary excretion of pentazocine, following its oral administration, was observed. Individual variations in the rate of metabolic oxidation of pentazocine are responsible for the variations in the urinary excretion of pentazocine (24 h cumulative). Smoking did not affect the metabolism of the drug. Pharmacokinetic analysis of the urinary excretion rate of pentazocine, using an open three compartment model, indicated that the fractional metabolic clearance is correlated with the cumulative urinary excretion (24 h) of the drug under conditions of acidic urinary pH. A g.l.c. method for the determination of pentazocine in urine is described.

The influence of smoking on the intersubject variation in pentazocine elimination.

“…These links between environment and pentazocine dosage requirements suggest that the oxidative enzymes responsible for pentazocine elimination are induced in smokers and urban subjects. In a previous study using only a small sample population, no distinct differences in the cumulative urinary excretion of orally administered pentazocine between smokers and non-smokers were observed (Vaughan & Beckett, 1974).…”

“…However, when the kidney tubular reabsorption of this weakly basic drug is minimized by maintenance of an acid pH, intra-subject variations in urinary elimination are negligible and the excretion of pentazocine is independent of urinary volume (Vaughan & Beckett, 1974, Vaughan, 1972.…”

“…Duplicate aliquots of the bulked urine samples were analyzed for pentazocine by the gas liquid chromatographic method of Vaughan & Beckett (1974).…”

“…Even under conditions of acidic urinary pH, designed to minimize intra-subject variations, the blood levels and cumulative urinary excretion of pentazocine show considerable inter-subject variations (Beckett, Kourounakis, Vaughan & Mitchard, 1970;Vaughan & Beckett, 1974). Recently, the inter-subject variations in pentazocine elimination have been attributed to individual variations in metabolic oxidation rates (Vaughan & Beckett, 1974).…”

“…Recently, the inter-subject variations in pentazocine elimination have been attributed to individual variations in metabolic oxidation rates (Vaughan & Beckett, 1974).…”