THE IMPACT OF LAG TIME ON THE ESTIMATION OF PHARMACOKINETIC PARAMETERS .1. ONE-COMPARTMENT OPEN MODEL

Lag time in pharmacokinetics corresponds to the finite time taken for a drug to appear in systemic circulation following extravascular admin istration. Lag time is a reflection of the processes associated with t he absorption phase such as drug dissolution and/or release from the d elivery system and drug migration to the absorbing surface. Failure to specify the lag time can lead to inappropriate or erroneous estimates of pharmacokinetic parameters. This has been demonstrated in the case of a one-compartment open model by the pharmacokinetic analysis of bi oequivalence data from a study involving the administration of propoxy phene napsylate to human volunteers. Subsequently, pharmacokinetic and statistical analyses of data obtained from a series of 49 simulations involving a wide range of absorption and elimination rate constants ( 0.05 to 5.00 and 0.01 to 0.95 hr-1, respectively) showed that lag time has a substantial effect on several primary and secondary pharmacokin etic parameters.