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Pharmacokinetic Predictions (pharmacokinetic + prediction)

Distribution by Scientific Domains
Medical Sciences75%

Selected Abstracts

Pharmacokinetic prediction for intravenous ,-lactam antibiotics in pediatric patients

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007
Kenji Shimamura
Abstract A method for predicting pharmacokinetics in pediatric patients for intravenous ,-lactam antibiotics is proposed. We focused on the allometric relationships of pharmacokinetic parameters with individual body weights (BW) in human including healthy adults and pediatric patients. Drug concentration data for 15 intravenous ,-lactam antibiotics were collected retrospectively from the published articles and the individual pharmacokinetic parameters were re-calculated. A mixed effect modeling (MEM) was applied for the allometric relationship for those ,-lactam antibiotics, and mean and variances of inter-drug variability for the allometric parameters and also variance for intra-drug (residual) variability were estimated. Then drug-specific allometric parameters were estimated by an empirical Bayesian method using the pharmacokinetic parameters for a drug only in healthy adults as observations, and finally the individual pharmacokinetic parameters in pediatric patients were predicted. The predictability of the method was evaluated by the leave-one-out method. We also demonstrated a method for simulating plasma concentration,time profiles in pediatric patients, and the predicted time,course curves generally coincided well with the actual plasma concentration data for the tested drugs. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3125,3139, 2007 [source]

Pharmacokinetic predictions in children by using the physiologically based pharmacokinetic modelling

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2008
F. Bouzom
Abstract Nowadays, 50,90% of drugs used in children have never been actually studied in this population. Consequently, either our children are often exposed to the risk of adverse drug events or to lack of efficacy, or they are unable to benefit from a number of therapeutic advances offered to adults, as no clinical study has been properly performed in children. Actually the main methods used to calculate the dose for a child are based on allometric methods taking into account different categories of age, the body weight and/or the body surface area. Unfortunately, these calculation methods consider the children as small adults, which is not the case. Physiologically based pharmacokinetics is one way to integrate the physiological changes occurring in the childhood and to anticipate their impact on the pharmacokinetic processes: absorption, distribution, metabolism and excretion/elimination. From different examples, the application of this modelling approach is discussed as a possible and valuable method to minimize the ethical and technical difficulties of conducting research in children. [source]

Safety, Efficacy, and Pharmacokinetic Overview of Low-Dose Daily Administration of Tadalafil

THE JOURNAL OF SEXUAL MEDICINE, Issue 7 2009
Rebecca Wrishko PhD
ABSTRACT Introduction., Several phosphodiesterase type 5 (PDE5) inhibitors are commercially available for the treatment of erectile dysfunction (ED). Development of the first once-daily alternative dosing regimen with a PDE5 inhibitor was motivated by the behavioral complexities associated with sexual intimacy. Aim., To provide an alternative dosing option for certain men who may benefit from the removal of the temporal linkage between administration of an ED therapy and sexual intimacy or for men and their partners who anticipate at least twice-weekly sexual activity. Methods., Pharmacokinetic predictions of tadalafil plasma concentrations were generated based upon empirical data following 20-mg, single-dose administration coupled with tadalafil usage patterns from as-needed clinical trials. To support the pharmacokinetic simulations and pharmacodynamic assumptions, clinical trials were conducted to demonstrate the efficacy and safety of once-daily, low-dose tadalafil 2.5 and 5 mg. Main Outcome Measures., Simulated tadalafil plasma concentrations and comparison with safety and efficacy measures from clinical trials. Results., Based upon pharmacodynamic and pharmacokinetic data, once-daily doses of tadalafil 5 mg were predicted to provide therapeutic concentrations that would be maintained throughout the 24-hour dosing interval. Additionally, for a subgroup of men who anticipate at least twice-weekly sexual activity and are currently taking tadalafil 20 mg, a reduction in daily tadalafil exposure was predicted. To support the hypothesis that low-dose, once-daily tadalafil may be a safe and effective treatment alternative, clinical trials were conducted to demonstrate the safety and efficacy of once-daily tadalafil 2.5 and 5 mg. These results were similar to those of historical as-needed studies evaluating tadalafil 10 and 20 mg. Conclusions., Consistent with pharmacokinetic predictions, data from clinical trials indicate that once-daily use of low-dose tadalafil is a safe and effective treatment for men with ED. Wrishko R, Sorsaburu S, Wong D, Strawbridge A, and McGill J. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med 2009;6:2039,2048. [source]