Effect of Alpha-Chloralose on Disposition and Pharmacological Action of Orally Administered Chlorzoxazone in Rats
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- KANEKO Ikue
- Faculty of Pharmaceutical Sciences, Kobe-Gakuin University
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- TAKEUCHI Yoshikazu
- Faculty of Pharmaceutical Sciences, Kobe-Gakuin University
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- FUKUMORI Yoshinobu
- Faculty of Pharmaceutical Sciences, Kobe-Gakuin University
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- FUKUDA Tomoaki
- Faculty of Pharmaceutical Sciences, Kobe-Gakuin University
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抄録
The pharmacodynamic behavior of orally administered chlorzoxazone (CZX) was studied in rats. From the time course of CZX plasma concentration data under alpha-chloralose (80 mg/kg, i. p.) anesthesia, it was found that CZX obeyed a one-compartment model with first-order absorption. The pharmacological response intensity of CZX on the crossed extensor reflex was closely related to the plasma concentration data via Hill's equation under alpha-chloralose (80 mg/kg) anesthesia, but not at a 150 mg/kg dose. The influence of alpha-chloralose at the latter dose on CZX pharmacokinetics and pharmacodynamics appeared to be due to the pharmacodynamic interaction of alpha-chloralose and CZX, thus suggesting that the pharmacokinetic and pharmacodynamic concept proposed by Smolen was not applicable to CZX's behavior at such a dose in rats. Under alphachloralose (80 mg/kg) anesthesia, the biophase compartment was determined to be identical to the central compartment using our proposed model. On the basis of the effect of anesthetics on drug behavior, one may select an appropriate anesthetic dose to evaluate the relationship between the plasma levels and the onset and duration of the drug action. At the higher dose of alpha-chloralose (150 mg/kg), the free fraction of CZX was increased and a possible enhancement in CZX action was suggested.
収録刊行物
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- Journal of pharmacobio-dynamics
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Journal of pharmacobio-dynamics 14 (8), 429-434, 1991-08
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詳細情報 詳細情報について
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- CRID
- 1571417127324282112
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- NII論文ID
- 110003637435
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- NII書誌ID
- AA00704585
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- ISSN
- 0386846X
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- 本文言語コード
- en
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- データソース種別
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- CiNii Articles