Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs

Abstract

The pharmacokinetics of netilmicin, gentamicin and tobramycin in plasma and in perilymph of guinea pigs were studied after a single i.v. injection of 40 mg/kg. Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the i.v. dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a 3-compartment open model. The disposition half-lives (t1/2) in plasma of the 3 antibiotics were comparable and within the following ranges: t1/2.alpha. of 0.09-0.16 h; t1/2.beta. of 0.88-1.01 h; and t1/2.gamma. of 7.87-8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all 3 antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph drug concentrations were 4.17, 8.05 and 6.78 .mu.g/ml and occurred at 1, 2 and 4 h for netilmicin, gentamicin and tobramycin, respectively. The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27) followed by gentamicin (0.39) and tobramycin (0.57). The differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin.