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The aims of this study were to evaluate the pharmacokinetics of doripenem (Finibax®, Doribax®, S-4661), a parenteral carbapenem antibiotic, in pediatric patients based on concentrations of doripenem in plasma after administration of 20 mg/kg two or three times daily and to evaluate the dosing regimens by using Monte-Carlo pharmacokinetic/pharmacodynamic simulations. Population pharmacokinetic analysis was performed by using 190 plasma concentrations of doripenem from 99 patients (2months - 13years old). The two-compartment model well described the doripenem plasma concentrations in pediatric patients. Body weight was found to be the most significant influential factor. Gender was also found to be a significant covariate although the effect was relatively small. Monte-Carlo simulations indicated that 20 mg/kg over I hour infusion would give 90% probability of target attainment for 40% of time above minimum inhibitory concentration (MIC) against Haemophilus influenzae and Streptococcus pneumoniae, major causative pathogens in pediatric infections, and that 40 mg/kg, the highest approved dose for Japanese pediatric patients, administered over 3 hours infusion achieved 98.6% against 8 μg/mL. The developed population pharmacokinetic model of doripenem and Monte-Carlo simulations for pediatric patients should provide useful information for understanding the pharmacokinetic and PK/PD characteristics of doripenem and for optimal treatment of pediatric patients.
This article was published in the following journal.
Name: Journal of pharmaceutical sciences
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In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993)
Registered nurses with graduate degrees in nursing who provide care to pediatric patients who are acutely or critically ill.
Ongoing scrutiny of a population (general population, study population, target population, etc.), generally using methods distinguished by their practicability, uniformity, and frequently their rapidity, rather than by complete accuracy.
The frequency of different ages or age groups in a given population. The distribution may refer to either how many or what proportion of the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine.
The number of males and females in a given population. The distribution may refer to how many men or women or what proportion of either in the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine.
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