Simultaneous tubular excretion and reabsorption of pindolol in man

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Abstract
The plasma concentrations of pindolol have been examined following the administration of single doses of 15 mg tablets to eight healthy male subjects. The apparent half-life of elimination in plasma (t1/2=4.05 h) and in urine (t1/2=3.21 h) was calculated using conventional pharmacokinetic methods. The renal clearance was estimated by plotting urinary excretion rates versus plasma concentrations; for all subjects these plots were curved. In addition to these graphical estimations, the plasma concentrations of pindolol and the urinary excretion data for each volunteer were simultaneously fitted using a one or two-compartment open body model; a computer program using non-linear regression algorithms was used. This procedure did not give an adequate fit to the data. Another type of data analysis, using a population — based model, permitted us to show that the renal elimination of pindolol in man comprises of two separate processes — tubular secretion and reabsorption, which was partially saturable under the experimental conditions. The theoretical relevance and clinical significance of these findings are discussed.