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Pharmacokinetic Analysis of Single- or Multiple-Dose Plasma Drug Concentration Data with a Microcomputer Using Multi-Fraction Absorption Models

1989; Elsevier BV; Volume: 78; Issue: 2 Linguagem: Inglês

10.1002/jps.2600780217

1520-6017

Kazuo Murata, Kozo Tagawa, Kazuo Noda, Masayoshi Samejima,

Drug Solubulity and Delivery Systems

A Basic program for multi-fraction absorption models was developed to link with another microcomputer program, MULTI, and was named MFA-MULTI. A main frame computer program SIMP, based on a simplex method using differential equations, was also operated using a microcomputer equipped with a FORTRAN compiler and a 8087 floating-point coprocessor. These two programs [MFA-MULTI and SIMP (M)] were applied to the analysis of plasma concentration data of several drugs with irregular absorption profiles. The results by MFA-MULTI and SIMP(M) for the single- or multiple-dose data were almost coincident with those obtained by a SIMP program. The result for nalidixic acid estimated using MFA-MULTI or PKM-MULTI was also compared. The plasma nalidixic acid concentration, with irregular absorption profiles due to characteristics of dissolution in the gastrointestinal tract, was found to be described by a two-fraction absorption model. The MFA-MULTI program was applied to the analysis of plasma cimetidine concentration data with double peaks in humans. Pharmacokinetic absorption behavior of a sustained-release preparation of theophylline after repetitive oral administration was adequately evaluated using MFA-MULTI. In addition, application of multi-fraction absorption models to population pharmacokinetics is discussed.