engleski

Calculation of Pharmacokinetic Parameters of Depot Drugs

Besides very rough approximations of Area Under Curve (AUC) parameter and second phase elimination constant all other pharmacokinetic parameters of depot drugs couldn't be calculated by conventional approaches like Levenberg - Marquardt, Newton or Quasinewton - based nonlinear regression. Consequently, by using software available on market developed for pharmacokinetic analyses one cannot reliably analyze pharmacokinetic properties of drugs with biphasic or multiphasic release. Until now only pharmacokinetic models that involve lag - phase as a source of singularity could be analyzed by conventional regression methods. There are two main problems involved: complex explicit form of pharmacokinetic model function and necessity for nonlinear piecewise regression. Solution to the first problem involves application of Dirac delta function that serves as a switch from one pharmacokinetic model function to another that evolves as a consequence of the second phase of drug release. Nonlinear regressions of three types - Levenberg - Marquardt, Genetic Algorithms and Simulated Annealing for analysis of merit functions that involve singularities will be discussed. As a result of biphasic release evolves completely new and also relevant pharmacokinetic parameter - starting time of second - phase release, though that parameter is also the most important cause of complexity of this kind of regression. Finally, new methods are applied in calculation of pharmacokinetic parameters of sustained- release ketoprofen preparations of two manufacturers. One-compartment model with absorption phase included is used as pharmacokinetic model. A comparison of results reveals significant differences between these two formulations and that is the goal of bioavailability study. Advances of different methods will be also discussed.

pharmacokinetic parameters; depot drugs

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