Pharmacokinetics of drugs in mutant Nagase analbuminemic rats and responses to select diuretics

Authors

  • Joo Hyun Lee,

    1. College of Pharmacy, Kyung Hee University, Seoul, South Korea
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  • Young-Joo Lee,

    1. College of Pharmacy, Kyung Hee University, Seoul, South Korea
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  • Euichaul Oh

    Corresponding author
    1. College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea
    • Correspondence

      Euichaul Oh, College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi-do 420-743, South Korea.

      E-mail: eoh@catholic.ac.kr

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Abstract

Objectives

To report (1) the pharmacokinetics of drugs that are mainly metabolized via hepatic cytochrome P450s (CYPs) or mainly excreted via the urine and bile, (2) the mechanism for the urinary excretion of drugs (such as glomerular filtration or renal active secretion or re-absorption), and (3) the diuretic effect of some loop diuretics in mutant Nagase analbuminaemic rats (NARs), an animal model for human familial analbuminaemia based on the pharmacokinetics of drugs reported in the literatures.

Key findings

In NARs, the changes in the time-averaged non-renal clearances (CLNRs) of drugs that are mainly metabolized via CYPs were explained in terms of changes in the hepatic intrinsic clearance (mainly because of changes in CYPs), free (unbound) fractions of drugs in the plasma (fp) and hepatic blood-flow rate (QH) depending on the hepatic excretion ratios of drugs.

Summary

The CLNR changes of drugs mainly metabolized via hepatic CYPs can be sufficiently explained by the three earlier mentioned factors. The plasma albumin (furosemide) or globulin (azosemide, bumetanide and torasemide) binding affects their diuretic effects.

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