Propranolol disposition in renal failure.

Abstract

1 Previous studies of propranolol disposition in renal failure have been conflicting.2 Using simultaneous administration of [:'H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine clearance 14.5 + 2.8 ml/min) but not on haemodialysis and patients on haemodialysis (creatinine clearance <5 ml/min). 3 The effect of haemodialysis on propranolol binding and free fraction was also examined. The percentage of propranolol unbound rose from 7. 1% to 9.9%. (P <0.001) 20 min following heparinization and beginning haemodialysis. This was accompanied by a large rise in free fatty acids from 0.567 ± 0.059 to 3.326 ± 0.691 ,umol/ml (P < 0.005). 4 The blood to plasma concentration ratios of propranolol were significantly higher in patients with renal failure (P < 0.02) and on haemodialysis (P < 0.001) and were significantly negatively correlated (P < 0.001) with the haematocrit. 5 Although the half-life of propranolol was significantly shortened in the patients with renal failure (P < 0.02), there was no change in the apparent liver blood flow, extraction ratio or the principal determinants of steady-state drug concentrations in blood namely oral and intravenous clearance from blood. 6 There is, therefore, no pharmacokinetic basis to adjust the dosage of propranolol in patients with renal failure.

The effect of chronic renal failure on drug metabolism and transport

“…These findings are in agreement with the animal data discussed earlier. Another investigator was not able to reproduce these findings in stable renal failure patients with creatinine clearance of approximately 15 ml/min [66]. These patients may have had enough residual renal function to prevent the inhibition of hepatic metabolism.…”

Predictions of the In Vivo Clearance of Drugs from Rate of Loss Using Human Liver Microsomes for Phase I and Phase II Biotransformations

“…Thus, the increased free fraction of midazolam, or lower protein binding value, increased clearance of the drug. On the other hand, the clearance of propranolol, a b-receptor antagonist, was shown to be unaffected by differences in protein binding and thus the amount of free drug (12). The effect of plasma protein binding on the clearance of drugs has been extensively discussed in the literature (13).…”

β-Blocker Dialyzability and Mortality in Older Patients Receiving Hemodialysis

“…Acebutolol, atenolol, and metoprolol have high dialyzablility, 4-9 whereas bisoprolol and propranolol have low dialyzablility. [10][11][12][13][14] This characteristic could theoretically affect patient outcomes by lowering the average plasma concentration achieved in patients receiving high-dialyzability agents. We conducted this study to test the hypothesis that among patients receiving long-term hemodialysis, initiation of high-dialyzability b-blockers was associated with higher risks of death and cardiovascular events compared with low-dialyzability b-blockers.…”