Developmental Pattern of Gentamicin Kinetics in Very Low Birth Weight (VLBW) Sick Infants

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Abstract
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 μg/ml and trough concentration of 0.5-2 μg/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 ≤ 7 (I), 8-30 (II) and ≥ 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 μg/ml for the first; 5.7 ± 1.2 and 1.3 ± 0.6 μg/ml for the second; 5.1 ± 0.8 and 1.1 ±0.6 μg/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 m^2 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 1 and II but significant differences were found for the above between CA III vs. CA I and II (p < 0.005). G clearance closely correlated with C clearance (r = 0.99, p < 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 < 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.