Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates
12/2017
Journal Article
Authors:
Le, J.;
Poindexter, B.;
Sullivan, J. E.;
Laughon, M. ;
Delmore, P.;
Blackford, M.;
Yogev, R.;
James, L. P.;
Melloni, C.;
Harper, B.;
Mitchell, J.;
Benjamin, D. K., Jr.;
Boakye-Agyeman, F.;
Cohen-Wolkowiez, M.
Volume:
40
Pagination:
103-108
Issue:
1
Journal:
Ther Drug Monit
PMID:
29271816
URL:
https://www.ncbi.nlm.nih.gov/pubmed/29271816
DOI:
10.1097/FTD.0000000000000466
Keywords:
Ampicillin/blood/*pharmacokinetics Chromatography, Liquid Dried Blood Spot Testing/*methods Female Humans Infant, Newborn Male Models, Biological Prospective Studies Tandem Mass Spectrometry
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 (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.
