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

The steady-state pharmacokinetics, renal function and quantitative beta 2-microglobulin (beta 2-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 greater than 1,000 g birth weight on the 18-hour schedule (p less than 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 less than 0.01), plasma clearance (p less than 0.01), and trough levels (p less than 0.001). Despite the frequent occurrence of gentamicin trough levels persistently greater than 2.0 micrograms/ml, renal function matured normally as serum creatinine progressively decreased (p less than 0.001) and creatinine clearance progressively increased (p less than 0.001) with advancing conceptional age. Urinary excretion of beta 2-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 less than 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 beta 2-microglobulinuria, did not occur.