Dosing regimen of gentamicin and the effect of antenatal steroids on clearance in preterm infants

Abstract

ObjectiveDetermine the gentamicin pharmacokinetic and pharmacodynamic (PK/PD) profiles of once daily dosing (ODD) versus every 18-hour (q18h) regimens and to characterize the effect of antenatal steroid on gentamicin clearance (GentCL).\n\nStudy DesignRetrospective cohort of preterm infants ([&le;]34 weeks gestation; [&le;]7 days) who received gentamicin for >48 hours from January 2005 to June 2007. Serum gentamicin peak and trough concentrations were determined, and PK/PD profiles calculated using standard noncompartmental methods.\n\nResult122 (63%) infants received ODD and 73 (37%) received q18h regimen. Desired gentamicin peak (5 to 12 mcg/mL) and trough (<2 mcg/mL) concentrations were achieved in 80% (95%CI, 72-86) on ODD vs. 47% (95%CI, 36-58) on q18h (p<0.001). Target drug exposure (AUC >72 mcg/mL/hr) was achieved in 73% (89/122) of infants on ODD vs. 22% (16/73) on q18h (p < 0.001). GentCL was significantly lower in those who receive antenatal steroid (37+/-8 mL/kg/hr vs. 42+/-13 mL/kg/hr, p=0.04) but not affected by postnatal indomethacin treatment (p>0.86).\n\nConclusionPK/PD profile of gentamicin is improved by ODD in preterm infants. GentCl was significantly less in infants exposed to antenatal steroids but not in those treated with indomethacin.