Gentamicin pharmacokinetics in newborn and 42-day-old male piglets

The pharmacokinetics of gentamicin was investigated in six newborn male piglets, aged from 4 to 12 h at the time of administration of the drug, and six 42-day-old castrated male piglets, that had been weaned for 2 weeks following a single intravenous bolus of 5 mg/kg. Gentamicin was measured in serum and in urine by a fluorescence polarization immunoassay. The serum concentration-time data were best described by a three-compartment open model. A rapid initial distribution phase (pi phase) was observed in every animal. The serum beta half-life (t 1/2 beta) was significantly longer in the newborn piglets (mean +/- SEM) (5.19 +/- 0.30 h) than in the older group (3.50 +/- 0.23 h) (P < 0.05). Mean residence time was similarly longer in younger piglets (6.62 +/- 0.57 h) than in older animals (2.86 +/- 0.11 h) (P < 0.05). The steady-state volume of distribution (Vdss) was significantly larger for younger pigs (0.785 +/- 0.036 L/kg) than in elder pigs (0.474 +/- 0.029 L/kg) (P < 0.05). Urinary gamma half-life (t 1/2 gamma u) was 72.66 +/- 10.78 h in the newborn piglets and 69.20 +/- 14.77 h in the 42-day-old animals. A urinary delta phase was observed in three of the 42-day-old piglets and gave a mean t 1/2 delta u of 232.01 +/- 14.55 h. Percentages of urinary recovery of the administered dose after 144 h were 94.18 +/- 1.01 and 94.04 +/- 1.12 in the newborn and 42-day-old animals, respectively. Serum gentamicin clearance was significantly lower in younger animals (0.121 +/- 0.007 L/h.kg) than in the 42-day-old group (0.166 +/- 0.010 L/h.kg). It is suggested that in the newborn piglets, the increase of Vd(SS) could be explained by a higher proportion of extracellular water while the lower clearance could be attributed to a reduced glomerular filtration capacity. Gentamicin dosage requirement in the newborn piglets would therefore have to be adjusted, in order to take into consideration the observed differences in the man values of these latter pharmacokinetic parameters.