Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants.

Published

Journal Article

Limited pharmacokinetic (PK) data of metronidazole in premature infants have led to various dosing recommendations. Surrogate efficacy targets for metronidazole are ill-defined and therefore aimed to exceed minimum inhibitory concentration of organisms responsible for intra-abdominal infections.We evaluated the PK of metronidazole using plasma and dried blood spot samples from infants ≤32 weeks gestational age in an open-label, PK, multicenter (N = 3) study using population PK modeling (NONMEM). Monte Carlo simulations (N = 1000 virtual subjects) were used to evaluate the surrogate efficacy target. Metabolic ratios of parent and metabolite were calculated.Twenty-four premature infants (111 plasma and 51 dried blood spot samples) were enrolled: median (range) gestational age at birth 25 (23-31) weeks, postnatal age 27 (1-82) days, postmenstrual age 31 (24-39) weeks and weight 740 (431-1466) g. Population clearance (L/h/kg) was 0.038 × (postmenstrual age/30) and volume of distribution (L/kg) of 0.93. PK parameter estimates and precision were similar between plasma and dried blood spot samples. Metabolic ratios correlated with clearance.Simulations suggested the majority of infants in the neonatal intensive care unit (>80%) would meet the surrogate efficacy target using postmenstrual age-based dosing.

Full Text

Duke Authors

Cited Authors

  • Cohen-Wolkowiez, M; Sampson, M; Bloom, BT; Arrieta, A; Wynn, JL; Martz, K; Harper, B; Kearns, GL; Capparelli, EV; Siegel, D; Benjamin, DK; Smith, PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network,

Published Date

  • September 2013

Published In

Volume / Issue

  • 32 / 9

Start / End Page

  • 956 - 961

PubMed ID

  • 23587979

Pubmed Central ID

  • 23587979

Electronic International Standard Serial Number (EISSN)

  • 1532-0987

International Standard Serial Number (ISSN)

  • 0891-3668

Digital Object Identifier (DOI)

  • 10.1097/INF.0b013e3182947cf8

Language

  • eng