Clin Pharmacokinet
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Review Meta Analysis
Impact of cytochrome P450 2C19 polymorphisms on citalopram/escitalopram exposure: a systematic review and meta-analysis.
Citalopram and escitalopram, selective serotonin reuptake inhibitors, are primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. However, the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified, especially with regard to the quantitative impact of the CYP2C19*17 allele. ⋯ This is the first meta-analysis based on a systematic review of accumulated information that addresses the relationship between CYP2C19 genotypes and the exposure to citalopram or escitalopram. All functional CYP2C19 genotype groups demonstrated significant effects on (es)citalopram exposure. The findings based on our pooled analysis are likely to help in understanding the inter-individual variability in the exposure to citalopram and escitalopram in psychiatric patients and to facilitate dose selection, particularly for the homozygous carriers of CYP2C19*2 or *3 (loss of function) and CYP2C19*17 (gain of function) alleles. The results could improve individualization of citalopram or escitalopram therapy and could also be used for physiologically based pharmacokinetic modeling as well as pharmacokinetic/pharmacodynamic modeling.
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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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Meta Analysis
Population pharmacokinetics meta-analysis of recombinant human erythropoietin in healthy subjects.
The aim of this analysis was to develop a population pharmacokinetic model to describe the pharmacokinetics of recombinant human erythropoietin (rHuEPO) in healthy subjects, after intravenous and subcutaneous administration over a wide dose range, and to examine the influence of demographic characteristics and other covariates on the pharmacokinetic parameters of rHuEPO. ⋯ The population pharmacokinetic model developed is suitable to describe the pharmacokinetic behaviour of rHuEPO after intravenous and subcutaneous administration in healthy subjects, over a wide dose range.
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Meta Analysis
Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis) in cancer patients.
To characterise the population pharmacokinetics of trabectedin (ET-743, Yondelis(R)) in cancer patients. ⋯ The integration of trabectedin pharmacokinetic data demonstrated linear elimination, dose-proportionality up to 1.8 mg/m(2) and time-independent pharmacokinetics. The pharmacokinetic impact of dexamethasone and sex covariates is probably limited given the moderate to large interindividual pharmacokinetic variability of trabectedin. The antiemetic and hepatoprotective effects are still a valid rationale to recommend dexamethasone as a supportive treatment for trabectedin.