Population Pharmacokinetic Analysis of Cefaclor in Healthy Korean Subjects

Abstract

The aims of this study were: (1) to perform population pharmacokinetic analysis of cefaclor in healthy Korean subjects, and (2) to investigate possible effects of various covariates on pharmacokinetic parameters of cefaclor. Although cefaclor belongs to the cephalosporin family antibiotic that has been used in various indications, there have been very few population studies on factors affecting its pharmacokinetics. Therefore, this study is very important in that effective therapy could be possible through a population pharmacokinetic study that explores effective covariates related to cefaclor pharmacokinetic diversity between individuals. Pharmacokinetic results of 48 subjects with physical and biochemical parameters were used for the population pharmacokinetic analysis of cefaclor. A one-compartment with lag-time and first-order absorption/elimination was constructed as a base model and extended to include covariates that could influence between-subject variability. Creatinine clearance and body weight significantly influenced systemic clearance and distribution volume of cefaclor. Cefaclor’s final population pharmacokinetic model was validated and some of the population’s pharmacokinetic diversity could be explained. Herein, we first describe the establishment of a population pharmacokinetic model of cefaclor for healthy Koreans that might be useful for customizing cefaclor or exploring additional covariates in patients.

Pharmacokinetics and safety of the two oral cefaclor formulations in healthy chinese subjects in the fasting and postprandial states

“…Cefaclor, a ß-lactam antibiotic, is a second-generation cephalosporin antibiotic ( Arsalan et al, 2017 ; Jeong et al, 2021 ). Cefaclor is considered as a broad-spectrum antibiotic that is effective against both Gram-positive and negative microorganisms such as Haemophilus influenzae and Klebsiella .…”

Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics

“…The population pharmacokinetic models of fexofenadine established considering OATP1B1 or 2B1 genetic polymorphisms were fully evaluated and validated visually or numerically using Phoenix NLME and R-software (R Foundation, Vienna, Austria). Evaluations of the model were performed using generally applied tools for population-scale drug quantification model validations [ [11] , [12] , [13] , [14] , [15] , [16] ]. Applied tools include GOF (including distribution of residuals), visual predictive check (VPC), bootstrapping, and normalized prediction distribution error (NPDE).…”

“…Population pharmacokinetic variability and modeling studies of drugs are very useful scientific approaches to finding effective dosage regimens based on quantitative predictions [ [11] , [12] , [13] ]. Consideration of efficacy and safety through identification of the pharmacokinetic diversity of fexofenadine among individuals will be a very important concern in clinical practice [ [14] , [15] , [16] ]. Depending on the continuous exposure of fexofenadine, the pharmacokinetic variability among individuals may obviously appear, and this may lead to failure to reach the appropriate therapeutic target range or side effects (common reported side effects of fexofenadine: headaches, feeling sleepy, dry mouth, feeling sick, and dizziness) due to excessive accumulation.…”

Structure-Based Analysis of Cefaclor Pharmacokinetic Diversity According to Human Peptide Transporter-1 Genetic Polymorphism

“…Past reports have suggested the importance of interpreting the inter-individual pharmacokinetic variation of cefaclor [7,8]. Even though the same formulation and dose of cefaclor are administered, significant differences in body exposure may occur between individuals, and this is closely related to the risk of treatment failure and resistance (due to the persistence of subtherapeutic drug concentrations in the blood) as well as the side effects (such as hypersensitivity, allergic reactions, gastrointestinal disturbances, and blood disorders) of cefaclor.…”