GENTAMICIN PHARMACOKINETICS IN NEWBORN AND 42-DAY-OLD MALE PIGLETS

The pharmacokinetics of gentamicin was investigated in six newborn mal e piglets, aged from 4 to 12 h at the time of administration of the dr ug, and six 42-day-old castrated male piglets, that had been weaned fo r 2 weeks following a single intravenous bolus of 5 mg/kg. Gentamicin was measured in serum and in urine by a fluorescence polarization immu noassay. The serum concentration-time data were best described by a th ree-compartment open model. A rapid initial distribution phase (pi pha se) was observed in every animal. The serum beta half-life (t(1/2 beta )) was significantly longer in the newborn piglets (mean +/- SEM) (5.1 9 +/- 0.30 h) than in the older group (3.50 +/- 0.23 h) (P < 0.05). Me an 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-s tate volume of distribution (V-dss) was significantly larger for young er pigs (0.785 +/- 0.036 L/kg) than in elder pigs (0.474 +/- 0.029 L/k g) (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-ol d piglets and gave a mean t(1/2 delta u) of 232.01 +/- 14.55 h. Percen tages 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 y ounger 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 pigle ts, the increase of V-d(ss) could be explained by a higher proportion of extracellular water while the lower clearance could be attributed t o a reduced glomerular filtration capacity. Gentamicin dosage requirem ent in the newborn piglets would therefore have to be adjusted, in ord er to take into consideration the observed differences in the mean val ues of these latter pharmacokinetic parameters.