Pharmacokinetic analysis of single- or multiple-dose plasma drug concentration data with a microcomputer using multi-fraction absorption models.
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.
Murata
K
K
Products Formulation Research Laboratory, Tanabe Seiyaku Company, Ltd., Osaka, Japan.
Tagawa
K
K
Noda
K
K
Samejima
M
M
D000284:Administration, Oral; D000493:Allopurinol / Q000493:pharmacokinetics; D001499:Bayes Theorem; D002927:Cimetidine / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000097:blood; D007408:Intestinal Absorption; D008838:Microcomputers; D008954:Models, Biological; D009268:Nalidixic Acid / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000097:blood*; D010599:Pharmacokinetics; D012044:Regression Analysis; D012984:Software; D013444:Sulfisoxazole / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D009268:Nalidixic Acid; D000493:Allopurinol; D013444:Sulfisoxazole; D002927:Cimetidine; D004110:Diltiazem