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Propranolol disposition in renal failure.
Author(s) -
Wood AJ,
Vestal RE,
Spannuth CL,
Stone WJ,
Wilkinson GR,
Shand DG
Publication year - 1980
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1980.tb00511.x
Subject(s) - propranolol , medicine , pharmacokinetics , renal function , free fraction , extraction ratio , renal blood flow , creatinine , pah clearance , endocrinology , urology , effective renal plasma flow , chemistry , chromatography , extraction (chemistry)
1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]‐ 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 less than 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 less than 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 mumol/ml (P less than 0.005). 4 The blood to plasma concentration ratios of propranolol were significantly higher in patients with renal failure (P less than 0.02) and on haemodialysis (P less than 0.001) and were significantly negatively correlated (P less than 0.001) with the haematocrit. 5 Although the half‐life propranolol was significantly shortened in the patients with renal failure (P less than 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.