Developmental pattern of gentamicin kinetics in very low birth weight (VLBW) sick infants

Kinetic studies were carried out in 15 very low birth weight (VLBW) infants during three courses of gentamicin (G) therapy for suspected sepsis. All received two courses but only 6 required a third course. G dosage was 2.0 +/- 0.2 mg/kg/24 h for the first and second course and 2.5 mg/kg/12 h for the third course. G dosage was adjusted to maintain serum peak G concentration of 4-8 micrograms/ml and trough concentration of 0.5-2 micrograms/ml. On the third day of therapy, a 24-hour collection of urine for creatinine (C) and G concentrations was performed in 28 of 36 cases. G clearance and G elimination rate constant were calculated based on chronological age (CA) of less than or equal to 7 (I), 8-30 (II) and greater than or equal to 31 (III) days. The mean BW and GA were 1,002 +/- 206 g and 28.4 +/- 1.5 weeks, respectively. Mean CA for the starting of therapy for each course was the first day, 19 +/- 9 and 68 +/- 26 days of life, respectively. Mean serum G peak and trough concentrations were 5.9 +/- 1.1 and 1.6 +/- 0.6 micrograms/ml for the first; 5.7 +/- 1.2 and 1.3 +/- 0.6 micrograms/ml for the second; 5.1 +/- 0.8 and 1.1 +/- 0.6 micrograms/ml for the third course of therapy. Mean apparent volume of distribution of G were 0.53 +/- 0.10 liter/kg for the first and 0.50 +/- 0.11 liter/kg for the second and third courses. Mean clearances for the three CA groups were 6.4 +/- 1.9; 7.6 +/- 3.2; 24.1 +/- 8.0 ml/min/1.73 m2 for G and 6.4 +/- 2.2; 7.7 +/- 3.1; 23.3 +/- 8.8 for C with serum C of 1.3 +/- 0.4, 1.2 +/- 0.6 and 0.6 +/- 0.4 mg%, respectively. There were no statistically significant differences for serum C, G and C clearance between CA I and II but significant differences were found for the above between CA III vs. CA I and II (p less than 0.005). G clearance closely correlated with C clearance (r = 0.99, p less than 0.001). The elimination rate constant was significantly higher after 30 days of life when CA III is compared to CA I and II or combined (p less than 0.001). This study shows that during the first month of life, VLBW sick infants still have decreased renal function and poor G clearance, therefore, G should be given every 24 h and the dose be adjusted based on individual patient serum G levels.