Radioreceptor Assay for Pharmacokinetic Studies of Glycopyrrolate

Kaila, Timo; Ali‐Melkkilä, T.; Iisalo, E; Kanto, J.

doi:10.1111/j.1600-0773.1990.tb00836.x

Cited by 17 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glycopyrrolate was determined from plasma with a sensitive radioreceptor assay using N-methylscopolamine as a radioligand described by Kaila et al (1990). The sensitivity of the assay for glycopyrrolate in plasma was 60 ng/l.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Oral Bioavailability of Glycopyrrolate in Children

Rautakorpi

Manner

Ali‐Melkkilä

et al. 1998

Pharmacology & Toxicology

View full text Add to dashboard Cite

Based on plasma levels determined with a radioreceptor assay and following a single oral (50 pgikg) and intravenous (5 pg/kg) administration of glycopyrrolate in six healthy children operated twice during a several weeks period, a negligible and variable oral bioavailability was found (3.3; 1.3-1 3.3%) (median;range). No significant changes in heart rate after oral or intravenous administration of the drug could be seen. Oral glycopyrrolate appears to have no place in paediatric premedication.Anticholinergic drugs have been commonly used in paediatric anaesthesia to prevent from harmful vagal reflexes and to avoid excessive secretions in the small airways (Mirakhur et al. 1978). The most effective way to attain these goals is intravenous administration of either atropine or glycopyrrolate briefly before induction of anaesthesia.Several authors have demonstrated that oral atropine (20 pg/kg) is an acceptable alternative to parenteral administration of anticholinergic premedication (Miller & Friesen 1988;Cartabuke et al. 1991), whereas oral glycopyrrolate (50 pg/kg) has only minor effects on heart rate and is less effective than orally administered atropine in attenuating bradycardia during induction of anaesthesia with halothane in infants and young children (Cartabuke et al. 1991). These clinical findings suggest a poor gastrointestinal absorption of glycopyrrolate. Because there is no knowledge of the bioavailability of oral glycopyrrolate and the related pharmacodynamics, we have evaluated this problem in clinical situations in children. Materials and MethodsThe study was approved by the Local Ethics Committee and informed written consent was obtained from the parents. The demographic data of the patients is shown in table 1.Six children, ASA physical status I, undergoing minor elective plastic or reconstructive surgery, were studied. Each patient was operated twice during a several weeks period. The duration of operation was 20-30 min. at both occasions. Glycopyrrolate premedication for the first operation was administered orally (50 pg/kg) in the recovery room 45 min. before induction of anaesthesia. For the second operation an intravenous dose of glycopyrrolate 5 pg/kg was administered to the same patient in the operating room 5 min. before induction of anaesthesia. Thus each patient could be used as hisher own control when the oral bioavailability of glycopyrrolate was calculated. A venous cannula was inserted into the forearm and a second venous cannula into the contralateral antecubital vein for serial venous blood samples ( 2 2 ml each). Blood samples were taken into K-EDTA plastic tubes just before and 2, 4, 6, 10, 15, 30, 60, 120, 180, 240, 360 and 480 min. after intravenous administration of glycopyrrolate and 30, 60, 120, 180, 360, 480 and 720 min. after oral administration of the drug. Plasma was separated and stored at -70" until analysis.Anaesthesia was induced with 3-5 mgikg thiopentone followed by 2-3 pg/kg fentanyl and 1.5 mgikg succinylcholine. Anaesthesia was maintained with N20/...

show abstract

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Oral Bioavailability of Glycopyrrolate in Children

Rautakorpi

Manner

Ali‐Melkkilä

et al. 1998

Pharmacology & Toxicology

View full text Add to dashboard Cite

show abstract

“…Animal studies indicate that it is metabolised via hydroxylation of the cyclopentyl ring and oxidation of the hydroxyl group in the mandelic acid residue (83). The derivatives of glycopyrrolate obtained by de-esterification and 3-hydroxylation of the aromatic ring do not interfere with the RRA (30). Studies using radiolabelled 3H-glycopyrrolate in humans indicate that 85% of the dose is excreted in the urine within 48 h and 80% of the radioactivity corresponds to the unchanged drug (58).…”

Section: Renal Excretion Of Anticholinergic Drugsmentioning

confidence: 99%

Pharmacokinetics and related pharmacodynamics of anticholinergic drugs

Ali‐Melkkilä

Kanto

Iisalo

1993

Acta Anaesthesiol Scand

Self Cite

153

View full text Add to dashboard Cite

The pharmacokinetics and some pharmacodynamic properties of atropine, glycopyrrolate and scopolamine are reviewed. With the development of new analytical methods for drug determination, it is now possible to measure relatively low concentrations of these drugs in biological fluids and, consequently, some new kinetic data have been collected. Following intravenous administration, a fast disappearance from the circulation is observed and due to a high total clearance value their elimination phase half-lives vary from 1 to 4 h. All these agents are nonselective muscarinic receptor antagonists, but their actions on various organ systems with cholinergic innervation show considerable diversity. The cardiovascular effects are of short duration; other peripheral muscarinic effects and CNS effects can last up to 8 h or even longer. Differing from atropine and scopolamine, glycopyrrolate as a quaternary amine penetrates the biological membranes (blood-CNS, placental barriers) slowly and incompletely, making it the drug of choice for elderly patients with coexisting diseases and for obstetric use. Similarly, its oral absorption is slow and erratic, and hence it cannot be used as an oral premedicant. Atropine, scopolamine and glycopyrrolate have a definitely faster absorption rate, when injected into the deltoid muscle compared with administration into the gluteal or vastus lateralis muscles. There appear to be significant differences in the metabolism and renal excretion of these agents. Scopolamine is apparently excreted into the urine mainly as inactive metabolites, nearly half of the atropine dose administered is recovered in the urine as the parent drug or as active metabolites and about 80% of glycopyrrolate is excreted as unchanged drug or active metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…Plasma samples were stored at -60 °C, and analyzed for scopolamine by using a radioreceptor assay (RRA) described originally for the analysis of an another anticholinergic drug, glycopyrrolate [10]. In the RRA, scopolamine competed with 0.5 nM tritiated N-methylscopolamine ( H-NMS, 83 Ci/mmol, New England Nuclear, Boston, MA., USA) for binding to muscarinic receptors obtained from rat brain.…”

Section: Scopolamine Analysismentioning

confidence: 99%

The effects of transdermal scopolamine on autonomic nervous activity during sleep

Alihanka

Lahdenperä

Kaila

1994

Eur J Clin Pharmacol

Self Cite

View full text Add to dashboard Cite

We studied the effect of transdermally applied scopolamine (scopolamine-TTS) on autonomic nervous activity during sleep. The double-blind, randomized, crossover study was carried out in six healthy male volunteers by applying 1.5 mg scopolamine-TTS or placebo patch on the retroauricular skin and by monitoring heart rate, cardiac ballistogram, respiration and body movements by using electrocardiogram and static charge sensitive bed. Scopolamine did not decrease the time the subjects desired to sleep (516 min after TTS, 511 min after placebo) or the number of body movements of 3-5 s duration the subjects spontaneously performed during sleep (47 after TTS, 58 after placebo). No adverse effects of scopolamine were reported spontaneously. Scopolamine-TTS slowed the mean heart rate during quiet sleep from 53.2 to 44.9 beats.min-1, and increased the duration of bradycardia in response to body movements (MIB-reflex) from 12.5 to 14.7 s with a significant difference between scopolamine and placebo effects. The bradycardias were not associated with disturbances in cardiorespiratory or central nervous system functions. The cardiac vagomimetic action of scopolamine-TTS could be explained by low plasma drug concentrations (175 pg/ml) primarily blocking only neuronal inhibitory prejunctional muscarinic receptors which regulate acetylcholine release from the autonomic ganglia and parasympathetic nerve-endings. Because of the central role of acetylcholine in the physiological regulation of sleep, the effect of scopolamine-TTS on sleep merits further investigations.

show abstract

Radioreceptor Assay for Pharmacokinetic Studies of Glycopyrrolate

Cited by 17 publications

References 17 publications

Pharmacokinetics and Oral Bioavailability of Glycopyrrolate in Children

Pharmacokinetics and Oral Bioavailability of Glycopyrrolate in Children

Pharmacokinetics and related pharmacodynamics of anticholinergic drugs

The effects of transdermal scopolamine on autonomic nervous activity during sleep

Contact Info

Product

Resources

About