Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man

Abstract

A study designed to investigate the relationship between the pharmacokinetics of digoxin and a measure of its pharmacological effect has been conducted. Serum digoxin concentrations and systolic time intervals were measured concurrently in 12 normal male volunteers following a 1.0 mg i.v. bolus injection. The averaged serum digoxin concentration- time and response-time data were analyzed pharmacokinetically using a three-compartment open model and nonlinear least- squares fitting. When only the serum level-time data were analyzed, a close relationship was found between calculated digoxin levels in the slowly distributing (deep) peripheral compartment and response of the heart to digoxin, as measured by changes in the QS₂ index δQS₂I. Although it was not possible to distinguish clearly a linear from a nonlinear relationship between digoxin levels in the deep compartment and δQS₂I, the nonlinear relationship gave the best overall fit when both serum digoxin and δQS₂I data were fitted simultaneously. The simultaneous fityielded a total body clearance of digoxin of 3.6 ml/min/kg and a terminal t_1/2 of 42 hr.