1987 Fiscal Year Final Research Report Summary
Quantitative analysis of factors determining age-related change in tissue distribution of animicrobial agents
| Project/Area Number |
61571094
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KANAZAWA UNIVERSITY |
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Principal Investigator |
TSUJI Akira FAC. PHARM. SCI., KANAZAWA UNIV. PROF., 薬学部, 教授 (10019664)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAI Ikumi FAC. PHARM. SCI., KANAZAWA UNIV. RESEARCH ASSISTANT, 薬学部, 助手 (20155237)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Tissue distribution / Peptide transport system / Organic anion transport system / Serum protein binding / Antimicrobial agent / <beta>-lactam antibiotics / cefazolin / セファゾリン |
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| Research Abstract |
The purpose of this study is to establish the pharmacokinetic method to predict quantitatively the change in the tissue distribution of drugs in relation to the change in the physiological and anatomical functions of tissues.
We have studied, about <beta>-lactam: antibiotics: 1. membrane transport mechanism in the small intestine, liver and kidney; 2. mechanism of the serum protein binding; 3. quantitative analysis for the factors determining the age-related change in the tissue distribution in animals and humans. The following results were obtained: 1. <beta>-lactam antibiotics can be recognized by and transported through the dipeptide carrier system(s) existing in the intestinal brush-border membrane; 2. In noneliminating organs, however, these antibiotics cannot transport cell membranes and localize within the interstitial fluid space and bind with albumin in this fluid. Based on this tissue distribution mechanism, the physiological pharmacokinetic model was developed to predict quantitatively the change in the tissue distribution of cefazolin, one of <beta>-lactam antibiotics, in 1-, 7-, 50-and 100-weeks-old rats; 3. Our theory verified in laboratory animals was applied to predict the volume of distribution at steady state for cefazolin in pediatric patients with bacterial infections. The change of indirect bilirubin to albumin molar ratio is predominantly responsible for the individual variation in the fraction unbound of cefazolin in plasma, which becomes the major factor determining the tissue distribution of this antibiotic in newborn infants.
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