Differential consequences of renal failure on the pharmacokinetics of Oxprenolol and its main metabolite

Abstract

Oxprenolol is a non-selective~-adrenoceptor blocking drug extensively metabolized in the liver. Forty milligrams of oxprenolol were given p.o. to 6 hemodialyzed patients and 7 healthy subjects. Blood concentration profiles of oxprenolol and of the glucuronide Of oxprenolol, the main blood derivative, were determined. Simultaneously the effect of the drug on exercise tachycardia was recorded.In patients with renal failure, both the area under the curve of blood concentration versus time and the peak blood concentrations were higher than in healthy subjects. Blood concentrations of oxprenolol decreased rapidly (mean half-life for patient 1.02 ± SD 0.40 h and for healthy subjects 1.26 ± 0.46 h). During the interdializis interval, there is, in practice, no elimination of glucuronide derivatives. Despite very high blood concentrations of oxprenolol glucuronide, no back transformation into active oxprenolol could be measured.A 40 mg dose of oxprenolol produced higher blood concentrations of oxprenolol in the patients than in the healthy subjects. Inspite of this, this dose did not result in any major difference in cardiac effect between patients and healthy subjects. Thus, administration of oxprenolol does not require dosage adjustement in patients with severe renal failure.

The Role of the Kidney in Drug Elimination: Transport, Metabolism, and the Impact of Kidney Disease on Drug Clearance

“…A somewhat clearer picture emerges for drugs eliminated primarily by glucuronidation. Comparative PK data in subjects with normal renal function and in patients with CKD and/or ESRD are available for diflunisal (a substrate of UGT1A9 and UGT2B7), ketoprofen, morphine, zidovudine (all UGT2B7 substrates), raloxifene (a UGT1A1 substrate, with a possible additional contribution of gut UGTs to presystemic metabolism), and oxprenolol (UGT enzyme(s) unknown) . CL total values are ∼40% to 60% lower in CKD patients ( Table ).…”