The impact of lag time on the estimation of pharmacokinetic parameters. I. One-compartment open model.
Lag time in pharmacokinetics corresponds to the finite time taken for a drug to appear in systemic circulation following extravascular administration. Lag time is a reflection of the processes associated with the absorption phase such as drug dissolution and/or release from the delivery 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 bioequivalence data from a study involving the administration of propoxyphene 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 pharmacokinetic parameters.
Nerella
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Pharmaceutics Division, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282.
Block
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LH
Noonan
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PK
D001702:Biopharmaceutics; D011431:Dextropropoxyphene / Q000493:pharmacokinetics; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics
D011431:Dextropropoxyphene