Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates

Ther Drug Monit. 2018 Feb;40(1):103-108. doi: 10.1097/FTD.0000000000000466.


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 (r = 0.902, analysis of variance P < 0.001). Using linear regression transformation, the estimated CONCPlasma (eCONCPlasma) was derived using (CONCDBS - 3.223)/0.51. The median bias and geometric mean ratio improved to -11% 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% (-11 to 50) and -8% (-34 to 11), respectively, when eCONCPlasma was used.

Conclusions: After transformation, DBS sampling accurately predicted ampicillin exposure in neonates.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Ampicillin / blood
  • Ampicillin / pharmacokinetics*
  • Chromatography, Liquid
  • Dried Blood Spot Testing / methods*
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Models, Biological
  • Prospective Studies
  • Tandem Mass Spectrometry


  • Ampicillin