Abstract

Evidence exists that the free plasma propranolol concentration may correlate with the pharmacological effect in a better way than the total plasma concentration. Three approaches to obtain the free fraction were compared,viz. 1) equilibrium dialysis, 2) calculation from the ratio erythrocyte concentration: plasma concentration ([R]/[P]-ratio) and 3) derivation from the salivary concentration. It is concluded that the [R]/[P]-ratio has a linear relationship to the free propranolol concentration, described by the equation [R]/[P]=6.9 (1-f)−0.25 (n= 46, r=+0.956; p<0.01). This method is reliable and simple to perform. No differences were seen between fresh blood samples, 14 days oldAcd-blood or artificial blood. The presence of various other drugs (4-hydroxypropranolol, chlorthalidone, clonidine, K-canrenoate, hydrallazine) did not interfere with the relationship between [R]/[P] and (1-f). A constant relationship between the salivary and free plasma propranolol concentrations does not exist, mainly because of buccal contamination. Equilibrium dialysis may pose an analytical problem. Therefore, the authors prefer the method based on the [R]/[P]versus (1-f) relationship.

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