Population Pharmacokinetics of Cis-, Trans-, and Total Cefprozil in Healthy Male Koreans

Abstract

Cefprozil, one of cephalosporin antibiotics, has been used extensively in clinics. However, pharmacokinetic (PK) information on cefprozil is still very limited. There have been no reports of population pharmacokinetics (PPKs). A PPK model for cefprozil will be a great advantage for clinical use. Thus, the aim of this study was to develop a PPK model for cefprozil for healthy male Koreans. Clinical PK and demographic data of healthy Korean males receiving cefprozil at a dose of 1000 mg were analyzed using Phoenix® NLME™. A one-compartment model with first-order absorption with lag-time was constructed as a base model. The model was extended to include covariates that influenced between-subject variability. Creatinine clearance significantly influenced systemic clearance of cefprozil. The final PPK model for cis-, trans-, and total cefprozil was established and validated. PPK parameter values of cis- and total cefprozil were similar to each other, but different from those of trans-isomer. Herein, we describe the establishment of accurate PPK models of cis-, trans-, and total cefprozil for healthy male Koreans for the first time. It may be useful as a dosing algorithm for the general population. These results might also contribute to the development of stereoisomeric cefprozil.

Population Pharmacokinetic Analysis of Cefaclor in Healthy Korean Subjects

“…This was related to the report that the activity of cytochrome P450 and phase II conjugation related to drug metabolism is increased with weight gain [27]. In addition, correlations between potential covariates and parameters used in the cefaclor population pharmacokinetic model shown in Figure 2 have also been reported in studies on pharmacokinetic analysis and modeling of other drugs [13,14]. Figure S1 shows graph results of those whose degrees of correlation were confirmed after those shown in Figure 2.…”

“…According to a previous report, cefaclor and cefprozil were mostly excreted in the urine through the kidney [20]. A correlation between CrCl and CL/F was confirmed in a population pharmacokinetic model of cefprozil for healthy adults, and that correlation was considered the main covariate [13]. For cefaclor, the correlation between CrCl and CL/F was reflected as the main covariate, similar to that found for cefprozil.…”

“…Construction and analysis of cefaclor's population pharmacokinetic model was performed using a non-linear mixed effects model with Phoenix nonlinear mixed effects model (NLME) software version 8.3 (Pharsight, Certara Inc.). Population pharmacokinetic analysis of drugs using this program has been actively performed [13,14]. Population pharmacokinetic model development for cefaclor was performed in the first-order conditional estimates method with extended least squares estimation (with N-ε interaction).…”

Pharmacokinetic Comparison between Methotrexate-Loaded Nanoparticles and Nanoemulsions as Hard- and Soft-Type Nanoformulations: A Population Pharmacokinetic Modeling Approach

“…Construction and analysis of the population pharmacokinetic model of methotrexate-loaded nanoparticles and nanoemulsions (and free methotrexate solution) were performed using a nonlinear mixed effects (NLME) model approach using Phoenix NLME (version 8.3, Pharsight, Certara Inc., Princeton, NJ, USA) software. This is a popular choice for population pharmacokinetic analysis of drugs [ 18 , 19 ]. Population pharmacokinetic model development was performed using the first-order conditional estimates method with extended least squares estimation (with ŋ – ε interaction).…”

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

“…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.…”