Abstract
The nonlinear tissue distribution of quinidine in rats was investigated by a physiologically based pharmacokinetic model. Serum protein binding of quinidine showed a nonlinearity over thein vivo plasma concentration range. The blood-to-plasma concentration ratio (C b/C p) of quinidine also showed a concentration dependence. The steady-state volume of distribution (V ss) determined over the plasma concentration range from 0.5 to 10 μg/ml was 6.0 ±0.45 L/kg. The tissue-to-plasma partition coefficient (Kp) of muscle, skin, liver, lung, and gastrointestinal tract (GI) showed a nonlinearity over thein vivo plasma concentration range of quinidine, suggesting saturable tissue binding. The concentration of quinidine in several tissues and plasma was predicted by a physiologically based pharmacokinetic model usingin vitro plasma protein binding and theC b/C p of quinidine. The tissue binding parameters were estimated fromin vivo Kp values. The predicted concentration curves of quinidine in each tissue and in plasma showed good agreement with the observed values.
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This study was supported by a grant-in-aid for Scientific Research provided by the Ministry of Education, Science and Culture of Japan.
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Harashima, H., Sawada, Y., Sugiyama, Y. et al. Analysis of nonlinear tissue distribution of quinidine in rats by physiologically based pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 13, 425–440 (1985). https://doi.org/10.1007/BF01061478
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DOI: https://doi.org/10.1007/BF01061478