Clin Pharmacokinet
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Review Meta Analysis
The relationship between drug clearance and body size: systematic review and meta-analysis of the literature published from 2000 to 2007.
A variety of body size covariates have been used in population pharmacokinetic analyses to describe variability in drug clearance (CL), such as total body weight (TBW), body surface area (BSA), lean body weight (LBW) and allometric TBW. There is controversy, however, as to which body size covariate is most suitable for describing CL across the whole population. Given the increasing worldwide prevalence of obesity, it is essential to identify the best size descriptor so that dosing regimens can be developed that are suitable for patients of any size. ⋯ To the best of our knowledge, this is the first study to have performed a meta-analysis of covariate relationships between CL and body size. Although many studies reported a linear relationship between CL and TBW, the average relationship was found to be nonlinear. LBW with an allometric exponent of ∼2/3 may be most suitable for describing an increase in CL with body size as it accounts for both body composition and allometric scaling principles concerning differences in metabolic rates across size.
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Multicenter Study Meta Analysis
Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic stem cell transplantation patients: towards individualized dosing.
The wide variability in pharmacokinetics of busulfan in children is one factor influencing outcomes such as toxicity and event-free survival. A meta-analysis was conducted to describe the pharmacokinetics of busulfan in patients from 0.1 to 26 years of age, elucidate patient characteristics that explain the variability in exposure between patients and optimize dosing accordingly. ⋯ The model-based individual dosing nomogram is expected to result in predictive busulfan exposures in patients ranging between 3 and 65 kg and thereby to a safer and more effective conditioning regimen for HSCT in children.
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The prevalence of obesity in adults and children is rapidly increasing across the world. Several general (patho)physiological alterations associated with obesity have been described, but the specific impact of these alterations on drug metabolism and elimination and its consequences for drug dosing remains largely unknown. In order to broaden our knowledge of this area, we have reviewed and summarized clinical studies that reported clearance values of drugs in both obese and non-obese patients. ⋯ Additionally, in obese patients, trends indicating higher clearance values were seen for drugs metabolized via CYP1A2, CYP2C9, CYP2C19 and CYP2D6, while studies on high-extraction-ratio drugs showed somewhat inconclusive results. Very limited information is available in obese children, which prevents a direct comparison between data obtained in obese children and obese adults. Future clinical studies, especially in children, adolescents and morbidly obese individuals, are needed to extend our knowledge in this clinically important area of adult and paediatric clinical pharmacology.