TY - JOUR AU - VATTIPALLI, MAHENDER AU - KODATI, DEVENDER AU - YELLU, NARSIMHA REDDY PY - 2014/09/01 Y2 - 2024/03/29 TI - Population Pharmacokinetics of Pioglitazone in South Indian Type-II Diabetic Patients JF - Asian Journal of Pharmaceutical and Clinical Research JA - Asian J Pharm Clin Res VL - 7 IS - 4 SE - Original Article(s) DO - UR - https://journals.innovareacademics.in/index.php/ajpcr/article/view/1442 SP - 102-105 AB - <p>Introduction: Population pharmacokinetics (PPK) is the study of this variability, its source and magnitude in populations. This information is used<br />to design dosage regimens that account for individual patient characteristics.<br />Objective: The objective of this study was to perform a non-linear mixed-effects analysis of the pharmacokinetics of pioglitazone, indicated for<br />treating diabetes and to study the effect of covariates such as age, body surface area and creatinine clearance on the PPK of pioglitazone in South<br />Indian diabetic patients.<br />Materials and Methods: A simple, rapid, and sensitive isocratic high-performance liquid chromatography-ultra violet method for detection and<br />quantification of pioglitazone in plasma had been developed. Intra- and inter-assay variations were &lt;1 and &lt;2% respectively. Recovery of pioglitazone<br />was 98-99%. A total of 137 blood samples for pioglitazone plasma concentration measurements following a single 15 mg dose of pioglitazone were<br />obtained from 43 subjects having age in between 18 and 75 years. The PPK model was built using NONMEM 7.2.0. The first-order (FO) and first-order<br />conditional estimation (FOCE) method was used to estimate base and covariate models for pioglitazone.<br />Results: One-compartment model with FO absorption and elimination (ADVAN 2 TRANS 2) was best-fit to the plasma concentration-time data<br />of pioglitazone. A combined error model was best-described the pattern of residual and between subject variability. The final model estimates of<br />clearance (CL) and volume (V) estimated by FOCE method were 3.4 lt/hr and 43 L.<br />Discussion: There were no past reports on PPK of pioglitazone. With covariate models, a significant decrease was observed in object function value,<br />between and within subject variability when compared with base model. The model found to best describe the data following the FOCE method was:<br />CL=CL=θ1*EXP ([η1] and V=θ2*EXP [η2]). These parameters are utilized for individualizing the loading and maintenance doses in diabetic patients.<br />No factor was found as informative covariate of pioglitazone.<br />Conclusion: In order to minimize the variability associated with drug exposure in Indian diabetic patients, the population parameter estimates were<br />given without influence of covariates.</p><p>Keywords: Covariate, Creatinine clearance, NONMEM, Pioglitazone, Residual variability.</p> ER -