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.
HOVI-WANDER M. Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study. Anesth Analg 1986;65:15-20.Midazolam, the first benzodiazepine derivative with watersoluble salts, was studied as an induction agent in general anesthesia for the elderly. In group 1 (n = 14), 5 or 10 mg oral diazepam was used as premedication, but in group 2 f n = 9), both oral (10 mgdixyrazin asa night-timesedative) and intramuscular (0.01 mglkg atropine + 1 mglkg meperidine) premedicants were used. Serum concentrations of benzodiazepines were determined using both gas-liquid chromatographic (unchanged rnidazolam) and radioreceptor assays (binding equivalents of benzodiazepines plus their active metabolites). In general, midazolam, 0.15 mglkg, intravenously resulted in smooth induction of anesthesia, although the time required for induction was rather long and a sudden but transient decrease in blood pressure was found in a significant number of patients. The course of anesthesia was otherwise satisfactory. A marked amnesic effect was observed, especially when diazepam was used as premedication. The pharmacokinetic parameters based on gas-liquid chromatographic measurements were quite comparable with those in young, healthy persons published earlier. In both groups, the binding equivalents measured with radioreceptor assay (reflecting total benzodiazepine activity) were higher than the levels of unchanged midazolani determined with gas-liquid chromatography. The relatively low dose of 0.15 mglkg of midazolam needed for anesthetic iizduction in the elderly indicates not pharmacokinetic, but pharrnacodynamic, alterations in older patients. We conclude that midazolam is a new intravenous induction agent for use in the elderly, but careful titration of the dosage according to the response of the patient is required. Diazepam premedication prior to midazolain causes a marked anterograde amnesic effect.
The antimuscarinic activity of oxybutynin was measured as oxybutynin equivalents by a radioreceptor assay (RRA). The activity was studied in plasma samples of five volunteers after a single oral dose (10 mg) or after a single intravenous dose (28 micrograms/kg) of oxybutynin hydrochloride. The results were compared to the concentrations of the drug measured by gas liquid chromatography (GLC). Following oral administration, the maximum concentration measured by RRA was significantly higher (706 nmol/l) than that by GLC (38 nmol/l). In contrast, equal concentrations were measured after intravenous administration by both methods. Metabolites with antimuscarinic activity are possibly formed through first-pass metabolism after orally administered oxybutynin. The total antimuscarinic activity of oxybutynin and its metabolites are measured by RRA, but only the parent drug by GLC.
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