Comparative analysis of ampicillin plasma and dried blood spot pharmacokinetics in neonates

Jennifer Le, Brenda Poindexter, Janice E. Sullivan, Matthew Laughon, Paula Delmore, Martha Blackford, Ram Yogev, Laura P. James, Chiara Melloni, Barrie Harper, Jeff Mitchell, Daniel K. Benjamin, Felix Boakye-Agyeman, Michael Cohen-Wolkowiez

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Dried blood spot (DBS) is a practical sampling strategy for pharmacokinetic studies in neonates. The utility of DBS to determine the population pharmacokinetics (pop-PK) of ampicillin, as well as accuracy versus plasma samples, was evaluated. Methods: An open-label, multicenter, opportunistic, prospective study was conducted in neonates. Ampicillin concentrations from plasma and DBS (CONCPlasma and CONCDBS) were measured by liquid chromatographic tandem mass spectrometry and analyzed using pop-PK and statistical (including transformation) approaches. Results: A total of 29 paired plasma and DBS samples from 18 neonates were analyzed. The median (range) gestational age and postnatal age were 37 (27-41) weeks and 8 (1-26) days, respectively. The geometric mean of CONCDBS to CONCPlasma ratio was 0.56. Correlation analysis demonstrated strong association between CONCPlasma and CONCDBS (r2 = 0.902, analysis of variance P < 0.001). Using linear regression transformation, the estimated CON-CPlasma (eCONCPlasma) was derived using (CONCDBS 2 3.223)/0.51. The median bias and geometric mean ratio improved to 211% and 0.88 (Wilcoxon signed-rank test, P < 0.001), respectively, when comparing eCONCPlasma to CONCPlasma. Furthermore, using pop-PK modeling, the median bias (interquartile range) for clearance and individual predicted concentrations improved to 8% (211 to 50) and 28% (234 to 11), respectively, when eCONCPlasma was used. Conclusions: After transformation, DBS sampling accurately predicted ampicillin exposure in neonates.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalTherapeutic drug monitoring
Volume40
Issue number1
DOIs
StatePublished - Feb 2018

Keywords

  • Ampicillin
  • Dried blood spot
  • Neonates
  • Pharmacokinetic modeling

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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