PMID- 29271816
OWN - NLM
STAT- MEDLINE
DCOM- 20181109
LR  - 20240502
IS  - 1536-3694 (Electronic)
IS  - 0163-4356 (Print)
IS  - 0163-4356 (Linking)
VI  - 40
IP  - 1
DP  - 2018 Feb
TI  - Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics 
      in Neonates.
PG  - 103-108
LID - 10.1097/FTD.0000000000000466 [doi]
AB  - 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.
FAU - Le, Jennifer
AU  - Le J
AD  - Skaggs School of Pharmacy, University of California, San Diego, San Diego, 
      California.
FAU - Poindexter, Brenda
AU  - Poindexter B
AD  - Indiana University School of Medicine, Indianapolis, Indiana.
AD  - Cincinnati Children's, Cincinnati, Ohio.
FAU - Sullivan, Janice E
AU  - Sullivan JE
AD  - Kosair Charities Pediatric Clinical Research Unit, Norton Children's Hospital, 
      University of Louisville, Louisville, Kentucky.
FAU - Laughon, Matthew
AU  - Laughon M
AD  - University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
FAU - Delmore, Paula
AU  - Delmore P
AD  - Wesley Medical Center, Wichita, Kansas.
FAU - Blackford, Martha
AU  - Blackford M
AD  - Akron Children's Hospital, Akron, Ohio.
FAU - Yogev, Ram
AU  - Yogev R
AD  - Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
FAU - James, Laura P
AU  - James LP
AD  - University of Arkansas for Medical Sciences, Arkansas Children's Hospital at 
      Little Rock, Little Rock, Arkansas.
FAU - Melloni, Chiara
AU  - Melloni C
AD  - Duke University Medical Center.
AD  - Duke Clinical Research Institute, Durham, North Carolina.
FAU - Harper, Barrie
AU  - Harper B
AD  - Duke Clinical Research Institute, Durham, North Carolina.
FAU - Mitchell, Jeff
AU  - Mitchell J
AD  - The EMMES Corporation, Rockville, Maryland.
FAU - Benjamin, Daniel K Jr
AU  - Benjamin DK Jr
AD  - Duke University Medical Center.
AD  - Duke Clinical Research Institute, Durham, North Carolina.
FAU - Boakye-Agyeman, Felix
AU  - Boakye-Agyeman F
AD  - Duke University Medical Center.
AD  - Duke Clinical Research Institute, Durham, North Carolina.
FAU - Cohen-Wolkowiez, Michael
AU  - Cohen-Wolkowiez M
AD  - Duke University Medical Center.
AD  - Duke Clinical Research Institute, Durham, North Carolina.
LA  - eng
GR  - HHSN267200700051C/HD/NICHD NIH HHS/United States
GR  - K24 HD058735/HD/NICHD NIH HHS/United States
GR  - U2C OD023375/OD/NIH HHS/United States
GR  - K23 AI089978/AI/NIAID NIH HHS/United States
GR  - U24 TR001608/TR/NCATS NIH HHS/United States
GR  - HHSN275201000003C/HD/NICHD NIH HHS/United States
GR  - HHSN275201000003I/HD/NICHD NIH HHS/United States
GR  - U54 HD090259/HD/NICHD NIH HHS/United States
GR  - HHSN272201500006C/AI/NIAID NIH HHS/United States
GR  - R01 HD076676/HD/NICHD NIH HHS/United States
GR  - HHSN272201300017C/AI/NIAID NIH HHS/United States
GR  - P50 HD090259/HD/NICHD NIH HHS/United States
GR  - HHSN272201300017I/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 7C782967RD (Ampicillin)
SB  - IM
MH  - Ampicillin/blood/*pharmacokinetics
MH  - Chromatography, Liquid
MH  - Dried Blood Spot Testing/*methods
MH  - Female
MH  - Humans
MH  - Infant, Newborn
MH  - Male
MH  - Models, Biological
MH  - Prospective Studies
MH  - Tandem Mass Spectrometry
PMC - PMC5764797
MID - NIHMS917090
COIS- Disclosures: The other authors have no potential conflicts of interest.
EDAT- 2017/12/23 06:00
MHDA- 2018/11/10 06:00
PMCR- 2019/02/01
CRDT- 2017/12/23 06:00
PHST- 2017/12/23 06:00 [pubmed]
PHST- 2018/11/10 06:00 [medline]
PHST- 2017/12/23 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - 10.1097/FTD.0000000000000466 [doi]
PST - ppublish
SO  - Ther Drug Monit. 2018 Feb;40(1):103-108. doi: 10.1097/FTD.0000000000000466.