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

Publication ,  Journal Article
Published in: Pediatric Infectious Disease Journal
January 1, 2013

Background: 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. Methods: 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. Results: 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 x (postmenstrual age/30)245 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. Conclusion: Simulations suggested the majority of infants in the neonatal intensive care unit (>80%) would meet the surrogate efficacy target using postmenstrual age-based dosing. © 2013 by Lippincott Williams & Wilkins.

Duke Scholars

Published In

Pediatric Infectious Disease Journal

DOI

EISSN

1532-0987

ISSN

0891-3668

Publication Date

January 1, 2013

Volume

32

Issue

9

Start / End Page

956 / 961

Related Subject Headings

  • Pediatrics
  • 3213 Paediatrics
  • 3202 Clinical sciences
  • 1117 Public Health and Health Services
  • 1114 Paediatrics and Reproductive Medicine
 

Citation

APA
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ICMJE
MLA
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Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants. (2013). Pediatric Infectious Disease Journal, 32(9), 956–961. https://doi.org/10.1097/INF0b013e3182947cf8
Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants.” Pediatric Infectious Disease Journal 32, no. 9 (January 1, 2013): 956–61. https://doi.org/10.1097/INF0b013e3182947cf8.
Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants.” Pediatric Infectious Disease Journal, vol. 32, no. 9, Jan. 2013, pp. 956–61. Scopus, doi:10.1097/INF0b013e3182947cf8.

Published In

Pediatric Infectious Disease Journal

DOI

EISSN

1532-0987

ISSN

0891-3668

Publication Date

January 1, 2013

Volume

32

Issue

9

Start / End Page

956 / 961

Related Subject Headings

  • Pediatrics
  • 3213 Paediatrics
  • 3202 Clinical sciences
  • 1117 Public Health and Health Services
  • 1114 Paediatrics and Reproductive Medicine