Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting: A prospective nonrandomized single-site study
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Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting : A prospective nonrandomized single-site study. / Amponsah, Seth K; Adjei, George O; Enweronu-Laryea, Christabel C; Bugyei, Kwasi A; Hadji-Popovski, Kosta; Kurtzhals, Jørgen; Kristensen, Kim.
In: Current Therapeutic Research, Vol. 84, 2017, p. e1-e6.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting
T2 - A prospective nonrandomized single-site study
AU - Amponsah, Seth K
AU - Adjei, George O
AU - Enweronu-Laryea, Christabel C
AU - Bugyei, Kwasi A
AU - Hadji-Popovski, Kosta
AU - Kurtzhals, Jørgen
AU - Kristensen, Kim
PY - 2017
Y1 - 2017
N2 - BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings.OBJECTIVES: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin.METHODS: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12 hours), were recruited. Serum amikacin concentration was measured at specified times after treatment initiation and analyzed using a population PK modeling approach.RESULTS: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n = 25), and preterm (<37 weeks' gestation n = 36) neonates were 6.2 (3.4) and 9.2 (5.7) µg/mL, respectively (P = 0.02). A 1-compartment model best fitted amikacin disposition, and birth weight was the most important predictor of amikacin clearance (CL) and distribution (V). The population CL and V of amikacin were related as CL (L/h) = 0.153 (birth weight/2.5)(1.31), V (L) = 2.94 (birth weight/2.5)(1.18). There was a high between-subject variability (58.9% and 50.7%) in CL and V, respectively. CL and V were 0.058 L/h/kg and 1.15 L/kg, respectively, for a mean birth weight of 2.1 kg, and the mean half-life (based on 1-compartment model), was 13.7 hours.CONCLUSIONS: The V and half-life of amikacin in this cohort varied from that reported in non-African populations, and the high trough and low peak amikacin concentrations in both term and preterm neonates suggest strategies to optimize amikacin dosing are required in this population.
AB - BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings.OBJECTIVES: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin.METHODS: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12 hours), were recruited. Serum amikacin concentration was measured at specified times after treatment initiation and analyzed using a population PK modeling approach.RESULTS: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n = 25), and preterm (<37 weeks' gestation n = 36) neonates were 6.2 (3.4) and 9.2 (5.7) µg/mL, respectively (P = 0.02). A 1-compartment model best fitted amikacin disposition, and birth weight was the most important predictor of amikacin clearance (CL) and distribution (V). The population CL and V of amikacin were related as CL (L/h) = 0.153 (birth weight/2.5)(1.31), V (L) = 2.94 (birth weight/2.5)(1.18). There was a high between-subject variability (58.9% and 50.7%) in CL and V, respectively. CL and V were 0.058 L/h/kg and 1.15 L/kg, respectively, for a mean birth weight of 2.1 kg, and the mean half-life (based on 1-compartment model), was 13.7 hours.CONCLUSIONS: The V and half-life of amikacin in this cohort varied from that reported in non-African populations, and the high trough and low peak amikacin concentrations in both term and preterm neonates suggest strategies to optimize amikacin dosing are required in this population.
U2 - 10.1016/j.curtheres.2017.01.001
DO - 10.1016/j.curtheres.2017.01.001
M3 - Journal article
C2 - 28761582
VL - 84
SP - e1-e6
JO - Current Therapeutic Research
JF - Current Therapeutic Research
SN - 0011-393X
ER -
ID: 181685108