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 was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been 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/l) in a 25 microliters 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 anaesthetized 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 1.7 +/- 0.71/kg and 15.4 +/- 10.3 vs 5.9 +/- 3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8 +/- 18.9 and 103.9 +/- 110.7 micrograms X h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.