Gentamicin disposition and effect on development of renal function in the very low birth weight infant

The steady-state pharmacokinetics, renal function and quantitative β₂-microglobulin (β₂-M) excretion were prospectively evaluated in 22 very low birth weight (VLBW) infants (700-1,470 g birth weight and 25-33 weeks gestational age) receiving 2.4 mg/kg gentamicin at randomly assigned 12- or 18-hour dosing intervals. Gentamicin trough concentrations were significantly lower in only those infants > 1,000 g birth weight on the 18-hour schedule (p < 0.05). ESTRIP analysis of gentamicin disposition at steady state revealed a biexponential function with half-life (mean ± SEM), 9.78 ± 0.86 h, plasma clearance 0.64 ± 0.06 ml/kg/min and volume of distribution 0.50 ± 0.03 liter/kg. Serum creatinine at steady state correlated with half-life (p < 0.01), plasma clearance (p < 0.01), and trough levels (p < 0.001). Despite the frequent occurrence of gentamicin trough levels persistently > 2.0 μg/ml, renal function matured normally as serum creatinine progressively decreased (p < 0.001) and creatinine clearance progressively increased (p < 0.001) with advancing conceptional age. Urinary excretion of β₂-M, thought to be a marker of proximal tubular damage from gentamicin, did not correlate with elevated trough levels, and was in fact lower in those infants with the highest measured trough levels (p < 0.001). Nephrotoxicity was suspected in only 2 infants both of whom had additional renal insult during the first few days of life. Despite the frequent occurrence of elevated gentamicin trough levels and prolonged elimination half-life in these VLBW infants, their renal function matured normally throughout therapy and nephrotoxicity from gentamicin, as evidenced by β₂-microglobulinuria, did not occur.