Clonidine in pediatric anesthesia : aspects on population pharmacokinetics, nasal administration and safety

摘要: Clonidine is widely use as premedication in pediatric patients and has many beneficial effects the perioperative period. The introduction of population pharmacokinetics 1980s proven useful when performing pharmacokinetic studies children to circumvent previous limitations with traditional pharmacokinetics. aim current thesis was further study (PK) pharmacodynamics (PD) clonidine setting. Population pharmacokinetics: In Study I PK-data after a bolus 1-2 microg•kg-1 41 were pooled data from 4 published studies. A PK analysis time–concentration profiles undertaken using nonlinear mixed modeling. this clarify children. Clearance at birth 3.8 l•h-1•70 kg-1 matured half-time 25.7 weeks reach 82% adult rate by 1 year age. relative bioavailability epidural rectal unity (F = 1). III estimate oral clonidine. plasma concentrations 8 undergoing adenotonsillectomy analysed. parameters calculated mixedeffects models. Current 2 intravenous found be 55.4% (CV 6.4%; 95% CI 46.9-65.4%). Nasal administration: II explore absorption nasal drops Plasma levels 9 administered following administration showed considerable interindividual variability delayed limited. aerosol increases spread drug cavity, thereby optimizing possibility for enhanced rapid well circumventing any possible first-pass that can associated administration. IV onset time preoperative sedation evaluated prospective, randomized, double-blind, controlled design including 60 receiving placebo, 3-4 or 7-8 respectively. At 45 min, adequate seen 65% both groups. Safety: One few its association reduced heart rate. V investigate incidence bradycardia premedicated either compared not pharmacologic premedication. On arrival operating room recorded. 507 included which 685 did receive (Group 0), 305 received iv CIV) 517 given CPO). Group 0 (0.15%; CI: 0-0.81%), CIV (0%; 0.00-0.98%) 5 CPO (0.97%; 0.31-2.24%) observed have HR < 85% 1st centile. Conclusions: neonates infants. It recommended reduce doses age-group. Oral adults. Our results suggest it would necessary administer least twice dose orally get similar effect low improve sedation. cannot if an ≤ 30 min desired. very low. Hence does appear rational refrain only due potential risk bradycardia. Inlaga.indd 3 8/10/2014 7:08:54 PM List publications This based upon papers, referred Roman numerals I–V. I. Potts AL, Larsson P, Eksborg S, Warman G, Lonnqvist PA Anderson BJ disposition children; analysis. Pediatric anaesthesia 2007; 17: 924-933. II. Almenrader N, Passariello M, Haiberger R, Pietropaoli S Absorption 2009; 19: 257-261. III. Nordlinder A, Bergendahl HT, PA, N 2011; 21: 335-340. IV. Onset aerosol: placebo-controlled, randomized trial. 2012; 22: 877-883. V. Incidence Manuscript.