Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition

Citation
Yg. Kim et al., Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition, LIFE SCI, 68(21), 2001, pp. 2329-2345
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
0024-3205 → ACNP
Volume
68
Issue
21
Year of publication
2001
Pages
2329 - 2345
Database
ISI
SICI code
0024-3205(20010413)68:21<2329:EOCOTP>2.0.ZU;2-A
Abstract
The effects of cysteine on the pharmacokinetics and pharmacodynamics of azo semide were investigated after intravenous (10 mg/kg) and oral (20 mg/kg) a dministration to male Sprague-Dawley rats fed on 23% protein diet (control rats), and 5% protein diet with (rats with PCMC) or without (rats with PCM) oral cysteine (250 mg/kg, twice daily for the fourth week) for 4 weeks. Af ter intravenous administration to rats with PCMC, some pharmacokinetic para meters restored fully or more than the level of control rats; the time-aver aged nonrenal clearance (2.70 versus 2.32 ml/min/kg) and apparent volume of distribution at steady state (160 versus 189 ml/kg) were comparable to tho se in control rats, however, the terminal half-life (34.7 versus 57.2 min) and mean residence time (73.3 versus 99.3 min) were significantly shorter, area under the plasma concentration-time curve from time zero to time infin ity (AUC, 1930 versus 2680 mug min/ml) was significantly smaller, and time- averaged renal (2.24 versus 1.21 ml/min/kg) and total body (CL, 4.98 versus 3.65 ml/min/kg) clearances were significantly faster than those in control rats, This could be mainly due to significantly faster renal clearance and at least partly due to increased cytochrome P450 1A2 activity by cysteine supplementation. After intravenous administration to rats with PCMC, the to tal amount of 8-hr urinary excretion of unchanged azosemide was significant ly greater (457 versus 305 mug/g body weight), however, the 8-hr urine outp ut (15.3 versus 31.1 ml/g kidney) was not significantly different between c ontrol rats and rats with PCMC. This could be due to the fact that urine ou tput seemed to reach an upper plateau from 10 mg/kg dose of azosemide in ra ts. (C) 2001 Elsevier Science Inc. All rights reserved.