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Effect of probenecid on the enantioselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit.

Martine Laethem, Frans Belpaire UGent, P Wijnant and Marcus Bogaert UGent (1995) PHARMACEUTICAL RESEARCH. 12(12). p.1964-1967
abstract
Purpose. To study the effect of probenecid on the stereoselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit. Methods. An oral dose of 50 mg!kg racemic oxprenolol was given to nine rabbits twice, in random sequence with and without the concurrent administration of probenecid. Oxprenolol enantiomers were determined in plasma and urine by an enantioselective HPLC method. Oxprenolol glucuronides were measured in plasma and urine after enzymatic hydrolysis. Results. The disposition of the oxprenolol enantiomers in rabbits is stereoselective, mainly due to a difference in metabolism. Renal excretion is only a minor elimination route for unchanged oxprenolol, and the renal clearances of the enantiomers are similar. Pretreatment with probenecid did not affect the plasma concentrations of the oxprenolol enantiomers, but there was a slight decrease in their urinary excretion. The plasma concentrations of the oxprenolol glucuronides are much higher than those of the parent enantiomers, and those of (S)-glucuronide are about twice those of its antipode. About 10% of the oxprenolol dose is excreted in the urine as glucuronides. The renal clearances of both glucuronides are similar, and markedly higher than the creatinine clearance. After probenecid, the mean glucuronide plasma levels were markedly higher, with for both glucuronides a more than twofold increase in mean AUC. Probenecid decreased the renal clearance of both glucuronides to about 30%. Moreover, it decreased slightly the formation clearance of (S)-glucuronide, while the formation clearance of (R)-glucuronide was not significantly influenced. Conclusions. Our results show that in the rabbit, both oxprenolol glucuronide diastereomers are actively secreted by the kidney, and that this process is inhibited by probenecid.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
oxprenolol glucuronides, enantioselectivity, oxprenolol, active renal secretion, pharmacokinetics, probenecid
journal title
PHARMACEUTICAL RESEARCH
Pharm. Res.
volume
12
issue
12
pages
1964-1967 pages
Web of Science type
Article
ISSN
0724-8741
language
English
UGent publication?
yes
classification
A1
id
186560
handle
http://hdl.handle.net/1854/LU-186560
date created
2004-01-14 13:41:00
date last changed
2013-12-09 15:41:35
@article{186560,
  abstract     = {Purpose. To study the effect of probenecid on the stereoselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit.
Methods. An oral dose of 50 mg!kg racemic oxprenolol was given to nine rabbits twice, in random sequence with and without the concurrent administration of probenecid. Oxprenolol enantiomers were determined in plasma and urine by an enantioselective HPLC method. Oxprenolol glucuronides were measured in plasma and urine after enzymatic hydrolysis.
Results. The disposition of the oxprenolol enantiomers in rabbits is stereoselective, mainly due to a difference in metabolism. Renal excretion is only a minor elimination route for unchanged oxprenolol, and the renal clearances of the enantiomers are similar. Pretreatment with probenecid did not affect the plasma concentrations of the oxprenolol enantiomers, but there was a slight decrease in their urinary excretion. The plasma concentrations of the oxprenolol glucuronides are much higher than those of the parent enantiomers, and those of (S)-glucuronide are about twice those of its antipode. About 10\% of the oxprenolol dose is excreted in the urine as glucuronides. The renal clearances of both glucuronides are similar, and markedly higher than the creatinine clearance. After probenecid, the mean glucuronide plasma levels were markedly higher, with for both glucuronides a more than twofold increase in mean AUC. Probenecid decreased the renal clearance of both glucuronides to about 30\%. Moreover, it decreased slightly the formation clearance of (S)-glucuronide, while the formation clearance of (R)-glucuronide was not significantly influenced.
Conclusions. Our results show that in the rabbit, both oxprenolol glucuronide diastereomers are actively secreted by the kidney, and that this process is inhibited by probenecid.},
  author       = {Laethem, Martine and Belpaire, Frans and Wijnant, P and Bogaert, Marcus},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keyword      = {oxprenolol glucuronides,enantioselectivity,oxprenolol,active renal secretion,pharmacokinetics,probenecid},
  language     = {eng},
  number       = {12},
  pages        = {1964--1967},
  title        = {Effect of probenecid on the enantioselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit.},
  volume       = {12},
  year         = {1995},
}

Chicago
Laethem, Martine, Frans Belpaire, P Wijnant, and Marcus Bogaert. 1995. “Effect of Probenecid on the Enantioselective Pharmacokinetics of Oxprenolol and Its Glucuronides in the Rabbit.” Pharmaceutical Research 12 (12): 1964–1967.
APA
Laethem, M., Belpaire, F., Wijnant, P., & Bogaert, M. (1995). Effect of probenecid on the enantioselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit. PHARMACEUTICAL RESEARCH, 12(12), 1964–1967.
Vancouver
1.
Laethem M, Belpaire F, Wijnant P, Bogaert M. Effect of probenecid on the enantioselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit. PHARMACEUTICAL RESEARCH. 1995;12(12):1964–7.
MLA
Laethem, Martine, Frans Belpaire, P Wijnant, et al. “Effect of Probenecid on the Enantioselective Pharmacokinetics of Oxprenolol and Its Glucuronides in the Rabbit.” PHARMACEUTICAL RESEARCH 12.12 (1995): 1964–1967. Print.