Population pharmacokinetics of vancomycin in Thai adult patients was determined by non-linear mixed-effects approach using 319 vancomycin serum concentrations from 212 patients. The data were best fitted by a two-compartment model and it was used to examine the effect of patient characteristics on the vancomycin pharmacokinetics. In the final model, there was a linear relationship between vancomycin clearance, CL (L/h), and creatinine clearance calculated by Cockcroft-Gault equation, CLCr (mL/min): CL  =0.044  ×  CLCr. Meanwhile, volume of central compartment, V 1 (L), was linearly related with the age (years old): V 1 = 0.542  × Age. Intercompartment clearance (Q) and volume of peripheral compartment (V 2) was 6.95 L/h and 44.2 L, respectively. The interindividual variability for CL, V 1, Q, and V 2 was 35.78, 20.93, 39.50, and 57.27%, respectively. Whereas, the intraindividual variability was 4.51 mg/L. Final model then was applied to predict serum vancomycin concentrations on validation group. Predictive performance revealed a bias of −1.43 mg/L (95% CI: −5.82–2.99) and a precision of 12.2 mg/L (95% CI: −1.60–26.16). In conclusion, population pharmacokinetic of vancomycin in Thai adult patients was developed. The model could be used to create vancomycin dosage regimen in the type of patient similar with the present study.

The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (< or = 32 week gestational age, < 1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/ kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL(L/h) = 0.0000610 x body weight (g) and CL (L/h) = 0.0000805 x body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd(L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.

Aims To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. Methods Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n= 108 samples, median two per patient; concentration: 14.8-170 ng ml −1 ) were fitted to a one-compartment model with first-order absorption and elimination in the NONMEM program using a logarithmic transformation of the observed and predicted concentrations. Fitting was achieved using the first order conditional estimation (FOCE) method with interaction between the interpatient and intrapatient variabilities. The interpatient variance of clearance (CL/F) and volume of distribution (V /F) and their covariance were estimated using an exponential error model. Intrapatient (residual) variance was estimated using an additive model. Results The clearance of cisapride was shown to be linearly related to current body weight, slope: 0.538. The typical population values of CL/F, V /F and Ka (absorption rate constant) were 0.538 l h −1 kg −1 , 21.9 l, and 2.58 h −1 , respectively.The population coefficients of variation (CV%) for CL/F and V /F were 34.4% and 84.3%, respectively. The squared coefficient of correlation between random effects for CL/F and V /F was 0.45. The intrapatient variance was 0.15. V /F and Ka were not influenced significantly by any patient characteristic. Conclusions Cisapride pharmacokinetics in infants with reflux disease were satisfactorily described by a one-compartment model. Current weight should be taken into account when calculating maintenance cisapride doses in these infants.

No abstract

No abstract