A radioreceptor assay for propranolol and 4-hydroxypropranolol.
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.
D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D001800:Blood Specimen Collection; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes; D011433:Propranolol / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D011941:Receptors, Adrenergic / Q000032:analysis*; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism
D001798:Blood Proteins; D007457:Iodine Radioisotopes; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C001422:4-hydroxypropranolol; D011433:Propranolol