Time-dependent oral absorption models

Kazutaka Higaki, S. Yamashita, G. L. Amidon

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The plasma concentration-time pro files following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka (t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data, The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model In conclusion, the incorporation of a time-dependent absorption rate coefficient ka (t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.

Original languageEnglish
Pages (from-to)109-128
Number of pages20
JournalJournal of Pharmacokinetics and Pharmacodynamics
Volume28
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Plasmas
Fluids
Kinetics
Propranolol
Oral Administration
Gastrointestinal Tract
Regression analysis
Regression Analysis
Pharmaceutical Preparations

Keywords

  • Absorption rate coefficient
  • Human
  • Propranolol
  • Time-dependent oral absorption

ASJC Scopus subject areas

  • Pharmacology
  • Catalysis
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Time-dependent oral absorption models. / Higaki, Kazutaka; Yamashita, S.; Amidon, G. L.

In: Journal of Pharmacokinetics and Pharmacodynamics, Vol. 28, No. 2, 2001, p. 109-128.

Research output: Contribution to journalArticle

Higaki, Kazutaka ; Yamashita, S. ; Amidon, G. L. / Time-dependent oral absorption models. In: Journal of Pharmacokinetics and Pharmacodynamics. 2001 ; Vol. 28, No. 2. pp. 109-128.
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