Stereoselective pharmacokinetics of oxprenolol and its glucuronides in humans*

✍ Scribed by Laethem, Martine E.; Lefebvre, Romain A.; Belpaire, Frans M.; Vanhoe, Hans L.; Bogaert, Marc G.

• Publisher: Nature Publishing Group
• Year: 1995
• Tongue: English
• Weight: 575 KB
• Volume: 57
• Category: Article
• ISSN: 0009-9236
• DOI: 10.1016/0009-9236(95)90211-2

✦ Synopsis

Stereoselective pharmacokinetics of oxprenolol and its glucuronides in humans

Object&e: To study the pharmacokinetics of R( + )-and S( -)-ox p renolol and their corresponding glucuronide conjugates in healthy subjects.

Metboak An oral dose of 80 mg racemic oxprenolol was given to eight male volunteers. Venous blood samples and urine were collected as a function of time. Oxprenolol enantiomers in plasma and urine were determined by an enantiospe&c HPLC method. Oxprenolol glucuronides in plasma and urine were measured as oxprenolol equivalents after enzymatic hydrolysis.

Redts: For R-oxprenolol the area under the plasma concentration-time curve was slightly higher (R/S ratio, 1.19) and the oral clearance slightly lower (R/S ratio, 0.84) than those parameters for S-oxprenolol.

The free fraction of R-oxprenolol in plasma was 4% higher than that of S-oxprenolol. The intrinsic clearance of S-oxprenolol was 1.5 times larger than that of R-oxprenolol, and a maximum of 3% of the dose was excreted as unchanged enantiomers in the urine. The plasma concentrations of S-oxprenolol glucuronide were more than three times higher than those of R-oxprenolol glucuronide. Twenty-five percent of the dose of the R-enantiomer was excreted in the urine as R-oxprenolol glucuronide; 29% of the S-enantiomer dose was excreted as S-oxprenolol glucuronide.

The renal clearance of R-oxprenolol glucnronide was, on average, 172 ml/mm, suggesting active tubular secretion. In contrast, the renal clearance of S-oxprenolol glucuronide was only 49 mllmin, which can be explained by the plasma binding of the compound.