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

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

Author information

1
Skaggs School of Pharmacy, University of California, San Diego, San Diego, California.
2
Indiana University School of Medicine, Indianapolis, Indiana.
3
Cincinnati Children's, Cincinnati, Ohio.
4
Kosair Charities Pediatric Clinical Research Unit, Norton Children's Hospital, University of Louisville, Louisville, Kentucky.
5
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
6
Wesley Medical Center, Wichita, Kansas.
7
Akron Children's Hospital, Akron, Ohio.
8
Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
9
University of Arkansas for Medical Sciences, Arkansas Children's Hospital at Little Rock, Little Rock, Arkansas.
10
Duke University Medical Center.
11
Duke Clinical Research Institute, Durham, North Carolina.
12
The EMMES Corporation, Rockville, Maryland.

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.

PMID:
29271816
PMCID:
PMC5764797
[Available on 2019-02-01]
DOI:
10.1097/FTD.0000000000000466
[Indexed for MEDLINE]

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