[Individual variability of pharmacokinetic parameters of amikacin in the elderly: retrospective studies]

In previous works, we have shown: i) good parameter predictive performances of the USC*PACK Clinical Programs for amikacin therapy in the elderly, ii) no significant difference generally detected between estimated parameter values at days 7 and 14 after the beginning of therapy, iii) assurance of neither accumulation nor toxicity during therapy up to 14 days or more, in our conditions. The objectives of this study were to explore which elements best explained differences found in the pharmacokinetic parameters (PK) of the elderly patients, who had received several courses of amikacin therapy.

patients' pharmacokinetic data and their medical records were retrospectively analyzed. Only patients who received amikacin therapy with at least a 2-month washout between their courses were studied. Two parameterizations of the 1-compartment PK model were used: one without covariates: Kel-Vol, where Kel = elimination rate constant and Vol = distribution volume, and another including covariates: Ks-Vs, with: Kel = Ks. CCr + Ki, where: Ks = renal fraction of Kel, Ki - non renal elimination, CCr = estimated creatinine clearance, and Vs = Vol/W, where Vs = distribution volume per kg and W = weight.

14 patients, 3 men and 11 women, fulfilled the criteria (4 of them satisfied the condition with 3 courses). They were 66 to 89 years old, their mean weight was 53.86 +/- 11.03 kg (46-71.5), their CCr averaged: 55.45 +/- 17.16 mL/min (14.84-96.27).

Among patients exhibiting changes (67%) in PK parameters between different courses of therapy, 42% could have the variability related to covariate (W, CCr) changes; in the others 58% the residual variability could be explained by different factors: severity of infection, immune system deficiency and/or particularly parenteral nutrition. Based on these result, we suggest including septic choc and parenteral nutrition as covariates during amikacin adaptive control.