The pharmacokinetics of drug distribution are evaluated for two types of drug administration, uiz., constant-rate intravenous infusion and instantaneous intravenous injection. Both modes of administration eventually result in a constant tissue compartmentcentral compartment distribution ratio of drug. However, the distribution ratio at pseudo-distribution equilibrium (after instantaneous intravenous injection) and at infusion equilibrium (some time after the start of infusion) are not equivalent. The consequence of this finding is that at equivalent plasma concentrations more drug will be in the tissue compartment during pseudo-distribution equilibrium than during infusion equilibrium although the total amount of drug which will enter the tissue compartment is independent of mode of administration. The present findings may have important implications for drug-distribution studies and with respect to the relative effectiveness of continuous and intermittent drug administration.
Keyphrases 0 Drug distribution-instantaneous versus constant rate i.v. administration 0 Model system-two compartment, open 0 Pharmacokinetics-instantaneous, constant-rate drug administration 0 Distribution ratios-pseudo-distribution, in-