[Changes in the pharmacokinetics of gentamycin during nephrotoxic therapy]

Nephrotoxicity secondary to aminoglycoside antibiotic therapy is a well-known complication in clinical medicine. We have analysed the influence of a 10-day gentamicin treatment with 3.40 mg/d on pharmacokinetic parameters and renal excretion of electrolyses and beta-NAG in 10 patients (9 female, 1 males) with UTJ. Using compartment-independent methods the following kinetic parameters at the first and 10th day of treatment were estimated: total body clearance from 100 to 80 ml/min (-20%), mean residence time from 2.7 to 3.5 h (+28%) and AUC from 6.7 to 9.4 mg/l.h (+41%). Similar results could be obtained using a linear two-compartment model: k13 is changed from 0.74 to 0.54 h-1 (-27%). Vdss approximately 16 1, k12 and k21 are not significantly influenced. There was no significant difference between the first and 10th day for renal excretion electrolyses, urine volume and osmolality with the exception of beta-NAG, which increased from 7.2 to 11.7 U/l (p less than 0.05). From the results it can be concluded that even a ten day gentamicin treatment with normal doses and serum concentrations in the therapeutic range less than 5 mg/l induce nephrotoxic effects at the glomerular and tubular side of the nephron. For quantification of the nephrotoxic effects we propose a nonlinear two-compartment model with a new pharmacokinetic parameter for renal damage. This new model allows to predict and to compare the nephrotoxic effects for different aminoglycoside antibiotics and different modes of treatment.