Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates

Abstract

According to our pharmacokinetic population model, initial doses of gentamicin of 10 mg/kg, and dosage intervals between 36-48 h, appear to be appropriate to achieve target peak and trough serum levels of 15-20 and <0.5 mg/L, respectively, when extended-interval dosage regimens are implemented in newborns. The half-life of gentamicin in premature babies of very low weight and gestational age <31 weeks is long. Thus, to achieve serum concentrations in the 1-10 mg/L range, the use of dosage regimens of 5 mg/kg at 36-48 h dosage intervals seems suitable.

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

“…This drug has a long t 1/2 and a large Vd, especially in premature infants [21]. The same applies to the other aminoglycosides.…”

“…There is a remarkable variation in the pharmacokinetic parameters of gentamicin [21,50], netilmicin [30][31][32]38], tobramycin [39,40] and amikacin [51,52]. Such a variation is due to renal maturation [50] as aminoglycosides are fairly water soluble and are eliminated with the urine.…”

“…This dose yields peak and trough concentrations which are 5-12 and <2 μg/ml respectively. Additionally, increasing the gentamicin dose to 5 mg/kg and extending the interval between doses to 24-48 h depending on the gestational age has been suggested [19][20][21][22]. The extended interval between doses yields peak values of gentamicin between 5 and 12 μg/ml and trough concentrations <2 μg/ml respectively, which are the expected values.…”

“…Later, it appeared that once-daily gentamicin dosing of 4-5 mg/kg yields higher peak and lower trough gentamicin concentration than twice-daily dosing [13][14][15][16] (for review see Rao et al [17] and Miron [18]). Recently, administering 5 mg/kg gentamicin and extending the dosing interval to 36-48 h has been recommended [19][20][21][22]. Extending the dosing interval to 48 h while increasing the gentamicin dose to 5 mg/kg causes an increase in peak concentration and a decrease in trough concentration as compared with a dose of 2.5 mg/kg every 12 h [20,22,23].…”

“…Using these dosing rates, gentamicin peak and trough concentrations should be <12 and <2 μg/ml respectively. Lanao et al [21] administered 10 mg/kg gentamicin every 36-48 h, and this dosage appeared to be appropriate to obtain the peak concentration of 15-20 μg/ml and the trough concentration <0.5 μg/ml.…”