COMPARISON OF RADIORECEPTOR ASSAY AND RADIOIMMUNOASSAY FOR ATROPINE - PHARMACOKINETIC APPLICATION

A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The Kd for binding was 0.48 nM and Bmax [maximum binding] was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine was compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyoscyamine, and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/1) in a 25 .mu.l serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anesthetized patients. The half-life calculated by the RRA was 3.7 .+-. 2.3 h (m .+-. SD) and by the RIA 4.3 .+-. 1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA (3.9 .+-. 1.5 vs. 0.71/kg and 15.4 .+-. 10.3 vs. 5.9 .+-. 3.6 ml/min per kg, respectively). The AUC [area under the concentration time curve] measured by the RRA and RIA was 29.8 .+-. 18.9 and 103 .+-. 110.7 .mu.g .times. h per l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.