An approach to predict the ductus-arteriosus dilating effect induced by lipo-prostaglandin E1 in newborn rats lacking plasma concentration-time data by the pharmacological response kinetic model

Keita Yamauchi, Shoji Yasunaga, Hiromu Kawasaki, Yuji Kurosaki

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2 Citations (Scopus)

Abstract

The usefulness of kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating effect (DADE) of lipo-PGE1 (a lipid emulsion preparation of prostaglandin E 1 for injection) preparations. Lipo-PGE1 was administered intravenously via the umbilical vein by a bolus injection or an infusion in newborn rats 60 min after the delivery. The DADE data were expressed as the inner diameter ratio between the ductus arteriosus and the main pulmonary artery, and were analyzed by a pharmacological response kinetic (PRK) model consisting of an Emax model and a simple pharmacokinetic model as the pharmacodynamic- and the pharmacokinetic-component, respectively. The latter component includes the release process of free-PGE1 from the lipid phase of lipo-PGE1, followed by distribution to the effect compartment. The Emax value was estimated by the maximal DADE observed 10 min after the bolus administration of each dose, and the value was fixed in the PRK analysis. The regression curves given by simultaneous non-linear least squares regression analysis were satisfactorily fitted to the observed DADE data at all doses. Prediction of the DADE of lipo-PGE1 in an infusion study was satisfactorily done using the estimated parameters in the i.v.-study. These findings indicate that PRK modeling based on the intensities of the observed pharmacological response-time data is a meaningful tool in some targeting-type drugs, for which pharmacokinetic analysis itself is meaningless or acquisition of pharmacokinetic data is technically impossible, in predicting the time courses of the drug's pharmacological response in different dosage regimens.

Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 2003

Fingerprint

Ductus Arteriosus
Alprostadil
Pharmacology
Pharmacokinetics
Prostaglandins E
Emulsions
Lipids
Injections
Umbilical Veins
Drug Delivery Systems
Least-Squares Analysis
Pulmonary Artery
Reaction Time
Regression Analysis
Pharmaceutical Preparations

Keywords

  • Ductus-arteriosus
  • Lipo-prostaglandin E
  • Newborn rat
  • Pharmacokinetic/ pharmacodynamic model
  • Pharmacological response kinetic model
  • Targeting-type drug

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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title = "An approach to predict the ductus-arteriosus dilating effect induced by lipo-prostaglandin E1 in newborn rats lacking plasma concentration-time data by the pharmacological response kinetic model",
abstract = "The usefulness of kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating effect (DADE) of lipo-PGE1 (a lipid emulsion preparation of prostaglandin E 1 for injection) preparations. Lipo-PGE1 was administered intravenously via the umbilical vein by a bolus injection or an infusion in newborn rats 60 min after the delivery. The DADE data were expressed as the inner diameter ratio between the ductus arteriosus and the main pulmonary artery, and were analyzed by a pharmacological response kinetic (PRK) model consisting of an Emax model and a simple pharmacokinetic model as the pharmacodynamic- and the pharmacokinetic-component, respectively. The latter component includes the release process of free-PGE1 from the lipid phase of lipo-PGE1, followed by distribution to the effect compartment. The Emax value was estimated by the maximal DADE observed 10 min after the bolus administration of each dose, and the value was fixed in the PRK analysis. The regression curves given by simultaneous non-linear least squares regression analysis were satisfactorily fitted to the observed DADE data at all doses. Prediction of the DADE of lipo-PGE1 in an infusion study was satisfactorily done using the estimated parameters in the i.v.-study. These findings indicate that PRK modeling based on the intensities of the observed pharmacological response-time data is a meaningful tool in some targeting-type drugs, for which pharmacokinetic analysis itself is meaningless or acquisition of pharmacokinetic data is technically impossible, in predicting the time courses of the drug's pharmacological response in different dosage regimens.",
keywords = "Ductus-arteriosus, Lipo-prostaglandin E, Newborn rat, Pharmacokinetic/ pharmacodynamic model, Pharmacological response kinetic model, Targeting-type drug",
author = "Keita Yamauchi and Shoji Yasunaga and Hiromu Kawasaki and Yuji Kurosaki",
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