Nonparametric Methods in Population Pharmacokinetics
JOURNAL OF CLINICAL PHARMACOLOGY
Authors: Goutelle, Sylvain; Woillard, Jean-Baptiste; Neely, Michael; Yamada, Walter; Bourguignon, Laurent
Abstract
Population pharmacokinetic (PK) modeling is a widely used approach to analyze PK data obtained from groups of individuals, in both industry and academic research. The approach can also be used to analyze pharmacodynamic (PD) data and pooled PK/PD data. There are 2 main families of population PK methods: parametric and nonparametric. The objectives of this article are to present an overview of nonparametric methods used in population pharmacokinetic modeling and to explain their specific characteristics to inform scientists and clinicians about their potential value for data analysis, simulation, dosage design, and therapeutic drug monitoring (TDM). Nonparametric methods have several interesting characteristics for population PK analysis, including computation of exact likelihoods, the ability to accommodate parameter probability distributions of any shape (eg, non-Gaussian), and to detect subpopulations and outliers. Nonparametric population methods are also highly relevant for model-based TDM and design of individualized drug dosage regimens. Several algorithms have been developed to estimate model parameter values within an individual and compute that individual's dosage to achieve target drug exposure with maximum precision and accuracy. Nonparametric modeling methods for both population and individual PK analysis are available under user-friendly packages.
Remarkable Removal of Antibiotic-Resistant Bacteria During Dairy Wastewater Treatment Using Hybrid Full-scale Constructed Wetland
WATER AIR AND SOIL POLLUTION
Authors: Abdel-Mohsein, Hosnia S.; Feng, Mengjia; Fukuda, Yasuhiro; Tada, Chika
Abstract
Effective treatment of dairy wastewater with efficient removal of antibiotic-resistant bacteria (ARB) is a great challenge for reuse of treated wastewater. Antibiotics are widely used in human and veterinary medicine, and antibiotics misuse has led to occurrence and spread of antibiotic-resistant bacteria (ARB). Reuse of treated wastewater for irrigation is a solution to deal with water shortage in developing countries. One of the major problems of treated wastewater reuse is the possible presence of ARB. Removal of ARB from dairy wastewater using a full-scale hybrid constructed wetland (CW) at Miyagi Prefecture, Japan, was studied. It was well-defined that hybrid CW caused a complete removal of ampicillin-, gentamicin-, kanamycin-, and streptomycin-resistant bacteria resulting in an effluent free of these resistant strains. Additionally, a significant decrease in the number of vancomycin-RB was definite with a final 3.2 log unit decrease in the effluent. This study addressed the remarkable efficiency of a full-scale hybridized CW in Kawatabi, Field Science Center, Tohoku University. It decreased the output of organic matter (COD), total suspended solids (SS), and ammonia-nitrogen. The performance of CW for the removal ARB from dairy wastewater was efficient to minimize the release of these contaminants into the environment and avoid the spread of antibiotic resistance with safe discharge and reuse of treated wastewater. Finally, the current study represents the first report about the assessment of ARB removal during treatment of dairy wastewater using CW.