Abstract
A radioreceptor assay for the measurement of propranolol and 4-hydroxypropranolol levels in plasma is described. Maximum sensitivity for propranolol was 1.2 +/- 0.15 ng/ml and for 4-hydroxypropranolol 4.2 +/- 0.4 ng/ml. Interassay and intra-assay variations for both were under 10%. Modifications in the radioreceptor assay permitted the measurements of total beta-adrenergic blocking activity and the separate contributions of parent drug and metabolite. When 4-hydroxypropranolol was stabilized, a composite level of total beta-adrenergic blocking activity in plasma was obtained. When the 4-hydroxy metabolite was oxidized, only the stable parent drug was detected. The difference in values between measurements made under these conditions was equivalent to the amount of 4-hydroxypropranolol in the sample. The radioreceptor assay was also used to measure the amount of free propranolol and 4-hydroxypropranolol. Under identical experimental conditions, more 4-hydroxypropranolol than propranolol circulated in the free form. These observations establish the feasibility of adapting the radioreceptor assay for propranolol to the measurement of total beta-adrenergic blocking activity and its components in plasma as well as to the measurement of free drug and metabolite levels.
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