Paediatric anaesthesia
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Paediatric anaesthesia · Mar 2011
Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: parallel shift in incorporating the knowledge of biological elements and increased applicability to drug development and clinical practice.
(i) To describe an example of the development work required for building a 'pediatric physiologically based pharmacokinetic' (P-PBPK) model (Simcyp Pediatric ADME Simulator), (ii) to replicate pediatric clinical studies and undertake theoretical studies to show the potential applications of mechanistic PBPK in pediatric drug clinical investigation and practice, with emphasis on pediatric anesthesia. ⋯ The examples highlight the use of prior knowledge of in vitro drug attributes and biology of the system (human body) to simulate PK and multiple DDI scenarios not infrequently encountered in critically ill pediatric patients.
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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
ReviewPropofol and children--what we know and what we do not know.
The pharmacokinetics of propofol are relatively well described in the pediatric population. Recent work has confirmed the validity of allometric scaling for predicting propofol disposition across different species and for describing pediatric ontogenesis. ⋯ Hence, questions relating to the comparative sensitivity of children to propofol, and differences in time to peak effect relative to adults, remain unanswered. K(eo) half-lives have been determined for pediatric kinetic models using time to peak effect techniques but are not currently incorporated into commercially available target-controlled infusion pumps.
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Paediatric anaesthesia · Mar 2011
ReviewCircadian rhythms and their development in children: implications for pharmacokinetics and pharmacodynamics in anesthesia.
The influence of time-of-day on the action and toxicity of drugs may be an important factor in the design of pharmacokinetic (PK) and pharmacodynamic (PD) studies, and the interpretation of data resulting from these studies. Time-of-day can have a profound influence on the action of drugs. In some settings (e.g. cancer chemotherapy), the timing of drug administration has been utilized to maximize therapeutic effect and minimize toxicity. ⋯ Circadian rhythms develop over the first months and years of life. Robust rhythms in hormone production (e.g. melatonin and cortisol) are seen at approximately 3 months of age, but it remains unclear as to when daily rhythms in drug PK and PD first appear. Here, we review the evidence for time-of-day effects in anesthetic drugs in adults and children and outline the potential influence this has on pediatric anesthesia.
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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.