The pharmacokinetics of
netilmicin in plasma and
blister fluid were compared in 10 healthy volunteers with normal renal function and 10 voluntary patients with varying degrees of renal impairment.
Netilmicin kinetics in plasma were characterized by an open two-compartment kinetic model. For the study of the kinetics of the
antibiotic in
blister fluid a specific kinetic distribution model was employed. In the healthy volunteers the plasma kinetics of
netilmicin showed a behaviour similar to that of other
aminoglycoside antibiotics, although a high
blister/plasma partition coefficient was obtained, with a mean value of 4.27 +/- 1.65. The transfer of
netilmicin in
blister fluid governed by the constants K1b/Vb and Kbl had mean values of 0.19 +/- 0.09 h-1 l-1 and 0.25 +/- 0.10 h-1, respectively. In the patients with renal impairment plasma and
blister fluid
antibiotic levels showed a progressive accumulation. In these patients the affinity of
netilmicin for
blister fluid was significantly altered. The
blister/plasma partition coefficient in this group of patients had a mean value of 2.65 +/- 1.33; the decrease being statistically significant (p = 0.023) with respect to the value obtained in the healthy volunteers. Similarly, the exit constant of
netilmicin from
blister fluid (Kb1) showed a statistically significant increase (p = 0.035) in the patients with renal impairment. The findings point to a loss of affinity of
netilmicin for
blister fluid as a result of renal impairment. Linear and logarithmic relationships were established between some pharmacokinetic parameters and
creatinine clearance. Dosage schedules are proposed for
netilmicin in patients with renal impairment.