Comparative study of different weighting methods in non-linear regression analysis: implications in the parametrization of carebastine after intravenous administration in healthy volunteers.
The influence of different weighting methods in non-linear regression analysis was evaluated in the pharmacokinetics of carebastine after a single intravenous dose of 10 mg in 8 healthy volunteers. Plasma concentrations were measured by HPLC using an on-line solid-phase extraction method and automated injection. The analytical method was fully validated and the function of the analytical error subsequently determined. The parametric approach was performed using different weighting methods, including the homoscedastic method (W = 1) and heteroscedastic methods using weights of 1/C, 1/C2, and the inverse of the concentration variance calculated through the analytical error function (1/V), and the results were statistically evaluated according to the normal distribution. Statistically significant differences were observed in the representative parameters of the disposition kinetics of carebastine. The use of a multiple comparison test for statistical analysis of all differences among group means indicated that differences were generated between the homoscedastic method (W = 1) and the heteroscedastic methods (1/C, 1/C2, and 1/V). The results obtained in the present study confirmed the utility of the analytical error function as a weighting method in non-linear regression analysis and reinforced the importance of the correct choice of weights to avoid the estimation of imprecise or erroneous pharmacokinetic parameters.
Jansat
J M
JM
Department of Pharmacokinetics and Drug Metabolism, Almirall-Prodesfarma, Barcelona, Spain.
Lastra
C F
CF
Mariño
E L
EL
D000328:Adult; D019540:Area Under Curve; D002090:Butyrophenones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D010600:Pharmacology / Q000706:statistics & numerical data*; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; C058251:carebastine