Structure-Related Pharmacokinetics of Xanthines after Direct Administration into the Peritoneal Cavity of Rats
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概要
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The pharmacokinetic characteristics, peritoneal permeability and hydrophobicity of three xanthine derivatives, theophylline, enprofylline and 1-methyl-3-propylxanthine (MPX), were investigated in rats. Isotonic saline (30 ml) containing xanthine (2.5,5 and 10 mg/kg) and blue dextran (0.2%) was administered intraperitoneally. The pharmacokinetic parameters of these xanthines were estimated using concentration-time data obtained from the peritoneal cavity and systemic circulation. Disappearance of these xanthines from the peritoneum declined in almost a monoexponential manner regardless of the dose administered. The volume of distribution (33.9 ml) in the peritoneal cavity was similar to the injection volume, indicating that dialysate was not diluted by the fluid in the peritoneal cavity and the effect of drug adsorption on the peritoneal membrane was minimal. The pharmacokinetics of MPX was dose-dependent, but that of theophylline and enprofylline was not. The fraction of the administered dose absorbed through the peritoneal cavity was 0.71,0.85,0.93 for theophylline, enprofylline and MPX, respectively. The peritoneal clearance was significantly different (p<0.05) among the three xanthines by two-way analysis of variance, and a strong correlation was noted between their peritoneal clearance and hydrophobicity (r=0.98,p<0.01). These findings suggest that hydrophobicity is an important determinant in the peritoneal permeation of these xanthines.
- 公益社団法人日本薬学会の論文
- 1997-10-15
著者
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HASEGAWA Takaaki
Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine
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Nabeshima Toshitaka
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, J
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KUZUYA Takafumi
Department of Hospital Pharmacy
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Nabeshima Toshitaka
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Nabeshima Toshitaka
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Meijo University
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Hasegawa Takaaki
Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine
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Hasegawa Takaaki
Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un
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Kobayashi Takaaki
Department Of Applied Immunology Nagoya University School Of Medicine
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SHIRAKI Rika
Department of Hospital Pharmacy, Nagoya University School of Medicine
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Shiraki Rika
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Shiraki Rika
Department Of Environmental Dermatology Nagoya University School Of Medicine
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Takagi Kenzo
Department Of Medical Technology Nagoya University School Of Health Sciences
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Hasegawa Takaaki
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Kuzuya T
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Nabeshima Toshitaka
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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HASEGAWA Takaaki
Department of Bacteriology, Nagoya University School of Medicine
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