INTRAINDIVIDUAL VARIABILITY OF PHARMACOKI NETIC PARAMETERS IN THE ELDERLY DURING AMIKACIN THERAPY - RETROSPECTIVE INVESTIGATIONS

In previous works, we have shown : i) good parameter predictive perfor mances of the USCPACK Clinical Programs for amikacin therapy in the e lderly, ii) no signifiant difference generally detected between estima ted 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 we re to explore which elements best explained differences found in the p harmacokinetic parameters (PK) of the elderly patients, who had receiv ed several courses of amikacin therapy. Methods: patients' pharmacokin etic data and their medical records were retrospectively analyzed. Onl y patients who received amikacin therapy with at least a 2-month washo ut between their courses were studied; Two parameterizations of the 1- compartment PK model were used : one without covariates : Kel-Vol, whe re Kel = elimination rate constant and Vol = distribution volume, and another including covariates : Ks-Vs, with : Kel = Ks. CCr + Ki,, wher e : Ks = renal fraction of Kel, Ki = non renal elimination, CCr = esti mated creatinine clearance, and Vs = Vol/W, where Vs = distribution vo lume per kg and W = weight. Results: 14 patients, 3 men and 11 women, fulfilled the criteria (4 of them satisfied the condition with 3 cours es). 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). Conclusion: Among patients exhibiting changes (67%) in PK parame ters between different courses of therapy, 42% could have the variabil ity related to covariate (W, CCr) changes; in the others 58% the resid ual variability could be explained by different factors : severity of infection, immune system deficiency and/or particularly parenteral nut rition. Based on these result, we suggest including septic choc and pa renteral nutrition as covariates during amikacin adaptive control.