| Autor: |
Kinowski, J.M., Rodier, M., Bressolle, F., Fabre, D., Augey, V., Richard, J.L., Galtier, M., Gomeni, R. |
| Zdroj: |
Journal of Pharmaceutical Sciences; March 1995, Vol. 84 Issue: 3 p307-311, 5p |
| Abstrakt: |
This study describes a methodology to calculatep‐aminohippurate (PAH) clearance (CL) and volume of distribution (V) with both the population parameters and one or two samples taken during the disposition and the elimination phase after a single intravenous infusion. The computer program P‐PHARM was used, and a log‐normal distribution and a heteroscedastic residual error distribution were assumed. Ninety‐six patients with and without renal insufficiency were available for analysis, and a two‐compartment model was used for data modeling. Population parameters were evaluated for 70 patients (mean number of observed concentration per individual, 6) by a three‐step approach. In step 1, the computer program was used to estimate the average pharmacokinetic parameters without taking into account the demographic and/or biological factors. In step 2, the relationship between the posterior individual estimates and the covariables was investigated with multiple linear stepwise algorithm. In step 3, the population parameters were re‐estimated considering the relationship with the covariables. From the regression performed in step 2, the following covariables were included: serum creatinine, body surface area, and body weight. The population averages ofCLandVwere 30.7 ± 2.36 L/h and 10.6 ± 1.29 L, respectively. To evaluate the predictive performance of the population parameters, the remaining 26 patients were used. The population parameters combined with one or two individual PAH plasma concentrations led to a bayesian estimation of individualCLandV. This estimation was compared with the classical procedure of parameter estimation (individual fitting from multiple blood samples). ForCLandV, bias was not statistically different from zero and the precision of these parameters was good. This procedure enables the estimation of individual pharmacokinetic parameters for PAH at minimal cost and minimal disturbance for the patient. |
| Databáze: |
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