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

S. Landers, P. L. Berry, G. L. Kearns, Sheldon Kaplan, A. J. Rudolph

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)285-302
Number of pages18
JournalDevelopmental Pharmacology and Therapeutics
Volume7
Issue number5
DOIs
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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