Once daily versus twice daily dosing of gentamicin in Thai neonates

Abstract

This study conducted in fifty-four neonates under 7 days of age at the Queen Sirikit National Institute of Child Health to investigate the serum gentamicin level, pharmacological responses and pharmacokinetic parameters after twice daily intravenous dosing versus once daily intravenous dosing; 27 neonates were given 2.0 - 2.5 mg/kg of gentamicin twice daily while 27 neonates were given 4.0 - 5.0 mg/kg of gentamicin once daily. The twice daily dosing group and the once daily dosing group 3ad mean steady state gentamicin peak concentrations of 5.94 ± 1.57 mg/l and 8.92 ± 1.59 mg/l, respectively (p<0.05) while their mean trough concentrations were 1.44 ± 0.49 mg/l and 0.90 ± 0.35 mg/l, respectively (p<0.05). There were 3 neonates (11.11%) in the twice daily dosing group whose peak and trough level were not within desimble therapeutic range, two patients with too high trough level (> 2mg/l) and one patient with subtherapeutic peak level (<4mg/l). Only one patient in the once daily group had undesirable trough level that พลร higher than1.5 mg/l but less than 2 mg/l. The mean pharmacokinetic parameters of the twice daily dosing group and the once daily dosing group were de:ermined as follow: the elimination rate constants were 0.137 ± 0.031 hr-1 and 0.105 ± 0.020 hr-1, respectively (p<0.05), the elimination half-life were 5.30 ± 1.23 hrs and 6.85 ± 1.36 hrs, respectively (p<0.05), the volume of distribution were 0.48 ± 0.13 l/kg and 0.54 ± 0.115 l/kg, respectively (p>0.05) and the clearance of gentamicin were 0.194 ± 0.068 l/hr and 0.167 ± 0.057 l/hr, respectively (p>0.05). Clearance of gentamicin had good correlation with postnatal age, weight, serum creainine concentration or creatinine clearance (r=0.84). Treatment with once daily dosing regimen did not present more nephrotoxicty than twice daily dosing regimen and even had the tendency to have less effect on renal function. Oice daily dosage regimen can achieve at least equivalent efficacy sompared to twice daily dosage regimen. All neonates in twice daily and once daily dosing groups flowed improvement in clinical outcome. The duration in once daily group showed tendency to be shorter than the twice daily group in nearly all diseases of gentamicin indication. Therefore once daily dosing of gentamicin with 4.0 - 5.0 mg/kg could be an appropriate regimen in term neonates.