Paediatric anaesthesia
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Pharmacokinetic (PK) and pharmacodynamic (PD) modeling has elucidated aspects of developmental pharmacology of value to the anesthetic community. The increasing sophistication of modeling techniques is associated with pitfalls that may not be readily apparent to readers or investigators. While size and age are considered primary covariates for PK models, the impact of birth on clearance maturation is poorly documented, dose in obese children is poorly investigated, pharmacologic implications of physiologic changes poorly portrayed, disease progression on drug response poorly depicted and the impact of metabolites on effect poorly illustrated. This review identifies some of these pitfalls and suggests ideas to circumvent or investigate these hazards.
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Paediatric anaesthesia · Mar 2011
Review Meta AnalysisDiclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years.
Diclofenac is an effective, opiate-sparing analgesic for acute pain in children, which is commonly used in pediatric surgical units. Recently, a Cochrane review concluded the major knowledge gap in diclofenac use is dosing information. A pharmacokinetic meta-analysis has been undertaken with the aim of recommending a dose for children aged 1-12 years. ⋯ Single doses of 0.3 mg·kg(-1) for intravenous, 0.5 mg·kg(-1) for suppositories, and 1 mg·kg(-1) for oral diclofenac in children aged 1-12 years are recommended as they yield a similar AUC to 50 mg in adults.
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Paediatric anaesthesia · Mar 2011
Randomized Controlled TrialKetorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months.
We determined the postoperative pharmacokinetics (PK), safety, and analgesic effects of ketorolac in 14 infants (aged <6 months) receiving a single intravenous (IV) administration of racemic ketorolac or placebo. ⋯ Stereo-isomer-specific clearance of ketorolac in infants (aged 2-6 months) shows rapid elimination of the analgesic S (-) isomer as reported in infants aged 6-18 months. No adverse effects were seen after a single IV ketorolac dose.
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Paediatric anaesthesia · Mar 2011
Review Case ReportsBuprenorphine TTS for children--a review of the drug's clinical pharmacology.
The transdermal therapeutic system (TTS) with buprenorphine is currently being used 'off-label' to treat chronic pediatric pain. We compiled available pharmacokinetic (PK), pharmacodynamic (PD), and clinical pediatric data on buprenorphine to rationalize treatment regimens. ⋯ Buprenorphine is of interest in pediatric postoperative pain and cancer pain control because of its multiple administration routes, long duration of action, and metabolism largely independent of renal function. There is little reason to expect buprenorphine effects in children out of infancy are fundamentally different to those in adults. From the limited pediatric data available, it appears that buprenorphine has no higher adverse potential than the more commonly used opioids. There is an urgent need for focused PK, PD, and safety studies in children before use in children becomes more widespread.
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Physiological-based pharmacokinetic models have been used to describe midazolam clearance (CL) maturation. There are no maturation descriptors of CL from neonate to adulthood based on reported estimates at different ages. ⋯ Previously published pharmacokinetic parameters can be used to develop maturation models that address gaps in current knowledge regarding the influence of age on a drug's disposition. If a midazolam sedation target concentration of 0.1 mg·l(-1) , similar to that given to adults, is assumed, then we might anticipate steady-state infusion rates of 0.014 mg·kg(-1) ·h(-1) in neonates, 0.05 mg·kg(-1) ·h(-1) in a 1-year-old, 0.06 mg·kg(-1) ·h(-1) in a 5-year-old and 0.05 mg·kg(-1) ·h(-1) in a 12-year-old child. Age-related pharmacodynamic differences that will affect dose and the impact of active metabolites on response are not yet quantified.