Skip to main content

Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design.

Publication ,  Journal Article
Tremoulet, A; Le, J; Poindexter, B; Sullivan, JE; Laughon, M; Delmore, P; Salgado, A; Ian-U Chong, S; Melloni, C; Gao, J; Benjamin, DK ...
Published in: Antimicrob Agents Chemother
June 2014

Although ampicillin is the most commonly used drug in neonates, developmental pharmacokinetic (PK) data to guide dosing are lacking. Ampicillin is primarily renally eliminated, and developmental changes are expected to influence PK. We conducted an open-label, multicenter, opportunistic, prospective PK study of ampicillin in neonates stratified by gestational age (GA) (≤ 34 or >34 weeks) and postnatal age (PNA) (≤ 7 or >7 days). Drug concentrations were measured by tandem mass spectrometry. PK data were analyzed using population nonlinear mixed-effects modeling in NONMEM 7.2. Monte Carlo simulations were conducted to determine the probability of target attainment for the time in which the total steady-state ampicillin concentrations remained above the MIC (T>MIC) for 50%, 75%, and 100% of the dosing interval. A total of 142 PK samples from 73 neonates were analyzed (median [range] GA, 36 [24 to 41] weeks; PNA, 5 [0 to 25] days). The median ampicillin dose was 200 (100 to 350) mg/kg/day. Postmenstrual age and serum creatinine were covariates for ampicillin clearance (CL). A simplified dosing regimen of 50 mg/kg every 12 h for GA of ≤ 34 weeks and PNA of ≤ 7 days, 75 mg/kg every 12 h for GA of ≤ 34 weeks and PNA of ≥ 8 and ≤ 28 days, and 50 mg/kg every 8 h for GA of >34 weeks and PNA of ≤ 28 days achieved the prespecified surrogate efficacy target in 90% of simulated subjects. Ampicillin CL was associated with neonatal development. A simplified dosing regimen stratified by GA and PNA achieves the desired surrogate therapeutic target in the vast majority of neonates.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

June 2014

Volume

58

Issue

6

Start / End Page

3013 / 3020

Location

United States

Related Subject Headings

  • Prospective Studies
  • Monte Carlo Method
  • Microbiology
  • Male
  • Infant, Premature
  • Infant, Newborn
  • Humans
  • Gestational Age
  • Female
  • Dose-Response Relationship, Drug
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tremoulet, A., Le, J., Poindexter, B., Sullivan, J. E., Laughon, M., Delmore, P., … Administrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network, . (2014). Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother, 58(6), 3013–3020. https://doi.org/10.1128/AAC.02374-13
Tremoulet, Adriana, Jennifer Le, Brenda Poindexter, Janice E. Sullivan, Matthew Laughon, Paula Delmore, Andrea Salgado, et al. “Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design.Antimicrob Agents Chemother 58, no. 6 (June 2014): 3013–20. https://doi.org/10.1128/AAC.02374-13.
Tremoulet A, Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, et al. Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother. 2014 Jun;58(6):3013–20.
Tremoulet, Adriana, et al. “Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design.Antimicrob Agents Chemother, vol. 58, no. 6, June 2014, pp. 3013–20. Pubmed, doi:10.1128/AAC.02374-13.
Tremoulet A, Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Salgado A, Ian-U Chong S, Melloni C, Gao J, Benjamin DK, Capparelli EV, Cohen-Wolkowiez M, Administrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network. Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother. 2014 Jun;58(6):3013–3020.

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

June 2014

Volume

58

Issue

6

Start / End Page

3013 / 3020

Location

United States

Related Subject Headings

  • Prospective Studies
  • Monte Carlo Method
  • Microbiology
  • Male
  • Infant, Premature
  • Infant, Newborn
  • Humans
  • Gestational Age
  • Female
  • Dose-Response Relationship, Drug