Influence of dose on the disposition kinetics of netilmicin in the isolated kidney of the rat.

The disposition of Netilmicin in the isolated rat kidney was studied in order to determine the influence of dose on the drug profile in this tissue. Doses of 50, 200, 800 or 10000 mg were injected through an afferent cannula into the isolated kidney as a bolus injection and outflow perfusate samples were collected. Statistical moments (AUC, MTT, VTT) were estimated from raw outflow curve data. Unit disposition function (UDF) was obtained by mass balance for each studied dose. The results of control assays addressing the viability of the isolated kidney preparations point to a high reproducibility for this preparation under the experimental conditions used, together with an acceptable viability. Comparison of statistical moments and derived parameters such as the extraction coefficient, distribution volume and drug renal clearance (E, Vd, ClE) suggest the existence of modifications in the distribution process with the dose, while elimination seems to remain unvariable; accordingly, the unit disposition function profiles were not superimposed for the different doses but differences during the early and final phases were observed.