Initial slope technique for estimation of the apparent volume of distribution during constant-rate intravenous...

A new technique is presented for estimating the apparent volume of distribution of drugs during constant-rate intravenous infusion. It is based on the initial slope of the plasma drug concentration versus time profile during the infusion. Equations are derived to provide estimates of the apparent volume of distribution for a one-compartment drug and for the central compartment of a two-compartment drug. The utility of the technique is illustrated by data obtained during constant-rate infusion of metronidazole in 11 healthy subjects. The average estimated value of the volume of the central compartment of metronidazole was 12% higher than the average value obtained by conventional pharmacokinetic analysis. The systematic error associated with this volume estimation procedure was assessed through the use of dimensionless concentration versus dimensionless time plots. The initial slope technique should prove useful in providing initial estimates of volume terms.