An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E_1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model
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概要
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The usefulness of kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating effect (DADE) of lipo-PGE_1 (a lipid emulsion preparation of prostaglandin E_1 for injection) preparations. Lipo-PGE_1 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 E_max model and a simple pharmacokinetic model as the pharmacodynamic- and the pharmacokinetic-component, respectively. The latter component includes the release process of free-PGE_1 from the lipid phase of lipo-PGE_1, followed by distribution to the effect compartment. The E_max 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-PGE_1 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.
- 2003-02-01
著者
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KAWASAKI Hiromu
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceut
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Komori Yukiko
岡山大学 大学院医歯薬学総合研究科
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Kawasaki Hiromu
Department Of Clinical Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmaceutic
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Kawasaki Hiromu
Graduate School Of Medicine Dentistry And Pharmaceutical Sciences Okayama University
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Kawasaki Hiromu
Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology Okay
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KUROSAKI Yuji
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Ok
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YAMAUCHI Keita
Department of Clinical Pharmaceutics and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Okaya
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Yamauchi Keita
Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology Okay
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Kurosaki Y
Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology Okay
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Kurosaki Y
The Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology
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Kurosaki Yuji
Department Of Clinical Pharmaceutical Science Faculty Of Pharmaceutical Sciences Okayama University
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Kurosaki Yuji
Department Of Clinical Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmaceutic
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YASUNAGA Shoji
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Ok
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Yasunaga Shoji
Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology Okay
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Kawasaki Hiromu
Department Of Clinical And Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmace
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Kurosaki Yuji
Department Of Clinical Pharmaceutical Science Faculty Of Pharmaceutical Sciences Graduate School Of
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