Pharmacokinetics and Oral Bioavailability of Glycopyrrolate in Children

Abstract

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/...

In Vitro–In Vivo Correlations Observed With Indacaterol-Based Formulations Delivered with the Breezhaler®

“…The measured oral bioavailabilities of indacaterol and glycopyrronium from the gastrointestinal tract are approximately 24% and 3%, respectively. (23,31,32) IVIVCs for indacaterol lactose blend (OnBrez Breezhaler)…”

“…(23,31) and a glycopyrronium bioavailability of 100% from the lungs and 3% from the gastrointestinal tract. (32) 1 In vitro total lung dose for indacaterol LB formulation in the Alberta idealized throat model were obtained using a square wave flow profile at a flow rate of 104 L min -1 , and a total volume of 2 L (n = 5).…”

“…(32) propionate are almost certainly due to in vitro testing that fails to utilize realistic throat models, and the effects of transient breath profiles on the different inhaler platforms. (39) Realistic throat models provide several advantages relative to standard NGI methods for assessing total lung deposition.…”

Case Report of Successful Treatment of Pallid Breath-Holding Spells With Glycopyrrolate

“…The mean time to reach maximum concentration was 90 minutes, with a mean bioavailability of 3.3%. 13 Originally synthesized in 1960, glycopyrrolate was used to treat peptic ulceration and has also been used during anesthesia for its effects as an antisialogue and to stabilize heart rate variability with reversal agents. 12,14 Like many drugs, glycopyrrolate affects multiple processes, owing to its actions on multiple receptors in different organs, such as the heart.…”

Evaluation of glycopyrrolate in the treatment of chronic drooling

“…Glycopyrrolate has poor oral availability at about 10%, and absorption is inhibited by food, particularly high-fat meals. 17 The solution for injection can be administered via enteral feeding tubes for those on nonoral feeding regimes if an oral liquid formulation is unable to be sourced. Glycopyrrolate has a rapid onset of effect: within 1-5 minutes when injected intravenously and within 15-30 minutes when given orally.…”