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 journalJournal articleResearchpeer-review

Harvard

Amponsah, SK, Adjei, GO, Enweronu-Laryea, CC, Bugyei, KA, Hadji-Popovski, K, Kurtzhals, J & Kristensen, K 2017, 'Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting: A prospective nonrandomized single-site study' Current Therapeutic Research, vol. 84, pp. e1-e6. https://doi.org/10.1016/j.curtheres.2017.01.001

APA

Amponsah, S. K., Adjei, G. O., Enweronu-Laryea, C. C., Bugyei, K. A., Hadji-Popovski, K., Kurtzhals, J., & Kristensen, K. (2017). Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting: A prospective nonrandomized single-site study. Current Therapeutic Research, 84, e1-e6. https://doi.org/10.1016/j.curtheres.2017.01.001

Vancouver

Amponsah SK, Adjei GO, Enweronu-Laryea CC, Bugyei KA, Hadji-Popovski K, Kurtzhals J et al. Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting: A prospective nonrandomized single-site study. Current Therapeutic Research. 2017;84:e1-e6. https://doi.org/10.1016/j.curtheres.2017.01.001

Author

Amponsah, Seth K ; Adjei, George O ; Enweronu-Laryea, Christabel C ; Bugyei, Kwasi A ; Hadji-Popovski, Kosta ; Kurtzhals, Jørgen ; Kristensen, Kim. / Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting : A prospective nonrandomized single-site study. In: Current Therapeutic Research. 2017 ; Vol. 84. pp. e1-e6.

Bibtex

@article{12c76feccc024a9abfa976d1bd00c2c1,
title = "Population pharmacokinetic characteristics of amikacin in suspected cases of neonatal sepsis in a low-resource African setting: A prospective nonrandomized single-site study",
abstract = "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.",
author = "Amponsah, {Seth K} and Adjei, {George O} and Enweronu-Laryea, {Christabel C} and Bugyei, {Kwasi A} and Kosta Hadji-Popovski and J{\o}rgen Kurtzhals and Kim Kristensen",
year = "2017",
doi = "10.1016/j.curtheres.2017.01.001",
language = "English",
volume = "84",
pages = "e1--e6",
journal = "Current Therapeutic Research",
issn = "0011-393X",
publisher = "Excerpta Medica, Inc.",

}

RIS

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

VL - 84

SP - e1-e6

JO - Current Therapeutic Research

JF - Current Therapeutic Research

SN - 0011-393X

ER -

ID: 181685108