دورية
Nonclinical Pharmacokinetic Evaluation of Desidustat: a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia
العنوان: | Nonclinical Pharmacokinetic Evaluation of Desidustat: a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia |
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المؤلفون: | Patel, Harilal, Modi, Nirav, Chaudhari, Jaimin, Patel, Prakash, Giri, Poonam, Patel, Hiren, Pandya, Vrajesh, Desai, Ranjit, Jain, Mukul |
المصدر: | European Journal of Drug Metabolism and Pharmacokinetics; September 2022, Vol. 47 Issue: 5 p725-740, 16p |
مستخلص: | Background and Objectives: Desidustat is a novel prolyl hydroxylase domain (PHD) inhibitor for the treatment of anemia. The objective of this study was to investigate the pharmacokinetics and drug–drug interaction properties of desidustat using in vitro and in vivo nonclinical models. Methods: In vitro, Caco2 cell permeability, plasma protein binding, metabolism, cytochrome P450 (CYP) inhibition, and CYP induction were examined. In vivo, pharmacokinetic studies of oral bioavailability in mice, rats, dogs and monkeys, dose linearity, tissue distribution, and excretion in rats were conducted. Results: In Caco-2 cells, the apparent permeability of desidustat was high at low pH and low at neutral pH. The oral bioavailability (%F) of desidustat was 43–100% with a median time to reach peak concentration (T |
قاعدة البيانات: | Supplemental Index |
تدمد: | 03787966 21070180 |
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DOI: | 10.1007/s13318-022-00788-3 |