Population pharmacokinetic study of gentamicin and a Bayesian approach in patients with renal impairment.
A population pharmacokinetic study was conducted on a total of 70 patients receiving gentamicin therapy. The patients included those with normal renal function and those with varying degrees of renal impairment. The parameters studied were the apparent volume of distribution and the plasma clearance of gentamicin. The interindividual variability and the residual variability of those parameters in the different subpopulations were studied according to a statistical model that assumed log normal distribution. Use of the one-way ANOVA test revealed statistically significant differences (P = 0.004) in the population plasma clearance of gentamicin in patients below and above 50 years of age. A linear relationship was established between the plasma clearance of gentamicin and the creatinine clearance in those patients. At the same time, the coefficient of variation of the Clp increased progressively in patients with renal impairment, varying between 28.98% in patients with a ClCR greater than 100 ml/min and 76.53% in patients with a ClCR between 20 and 60 ml/min. The results obtained in the population study were later applied to drug monitoring in 23 patients with varying degrees of renal function and who received gentamicin therapy with different doses. The residual variability of the population allowed us to calculate a weighting factor (FF) between the experimental and the population data using Bayesian fitting. The weighting factor was 0.89 in patients with normal renal function and 0.80 in patients with renal impairment. Statistical comparison of the pharmacokinetic parameters obtained from the populational data, non-linear regression and the Bayesian method using revealed differences in the values for the apparent volume of distribution obtained with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacy, Faculty of Pharmacy, University of Salamanca, Spain.
J M
JM
Lanao
A
A
Berrocal
M V
MV
Calvo
M
M
Perez
B
B
de la Calle
A
A
Domínguez-Gil
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D003404:Creatinine / Q000097:blood; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
D005839:Gentamicins; D003404:Creatinine