A new pharmacokinetic model including in vivo dissolution and gastrointestinal transit parameters.
When dissolution is the rate-limiting step in absorption of a drug, both it and gastrointestinal transit can play dominant roles in determining absorption. Therefore, a pharmacokinetic model including the process of dissolution, gastrointestinal transit rate and gastrointestinal pH profile was proposed to explain the behavior of drug formulations in vivo. Clarithromycin (CAM), which exhibits pH-dependent solubility and has high partition coefficients, was used as a drug to test the model, and the effect of a meal on serum concentrations of CAM after a single oral administration to healthy volunteers was evaluated. The results of pharmacokinetic analyses of serum concentration-time data for a single oral administration of CAM to humans in the fasting and postprandial states were well fitted by the new pharmacokinetic model. By substituting the pharmacokinetic parameters obtained into the model equations, the in vivo rate of dissolution could be determined. Pharmacokinetic parameters affecting drug bioavailability were also examined using the model. Factors influencing the behavior of a drug formulation in the gastrointestinal tract were determined. These findings indicate that the model we have proposed can be used to evaluate the behavior of drug formulations in vivo.
Ishii
K
K
Department of Pharmaceutics, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Katayama
Y
Y
Itai
S
S
Ito
Y
Y
Hayashi
H
H
D017291:Clarithromycin / Q000737:chemistry / Q000493:pharmacokinetics; D018565:Food-Drug Interactions; D005772:Gastrointestinal Transit / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008954:Models, Biological; D010599:Pharmacokinetics; D012995:Solubility
D017291:Clarithromycin