Format

Send to

Choose Destination
Br J Clin Pharmacol. 2016 Sep;82(3):754-61. doi: 10.1111/bcp.13001. Epub 2016 Jun 3.

Salivary caffeine concentrations are comparable to plasma concentrations in preterm infants receiving extended caffeine therapy.

Author information

1
Pediatrics, Tripler Army Medical Center, Honolulu, HI, USA.
2
Pediatrics, Uniformed Services University, Bethesda, MD, USA.
3
Clinical Pharmacology, Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
4
Newborn Medicine and Respiratory Diseases, Boston Children's Hospital, Boston, MA, USA.
5
Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
6
Slone Epidemiology Center, Boston University, Boston, MA, USA.
7
American SIDS Institute, Naples, FL, USA.
8
Pediatrics, University of Arkansas, Little Rock, AR, USA.
9
Biostatistics, Boston University School of Public Health, Boston, MA, USA.
10
Pediatrics, George Washington University, Washington, DC, USA.

Abstract

AIMS:

Caffeine concentrations in preterm infants are usually measured in the blood. However, salivary assays may provide a valid and practical alternative. The present study explored the validity and clinical utility of salivary caffeine concentrations as an alternative to blood concentrations and developed a novel plasma/salivary caffeine distribution model.

METHODS:

Paired salivary and plasma samples were obtained in 29 infants. Salivary samples were obtained using a commercially available salivary collection system. Caffeine concentrations in the saliva and plasma were determined using high-performance liquid chromatography. A population pharmacokinetic (PK) model was developed using NONMEM 7.3.

RESULTS:

The mean (± standard deviation) gestational age (GA) at birth and birth weight were 27.9 ± 2.1 weeks and 1171.6 ± 384.9 g, respectively. Paired samples were obtained at a mean postmenstrual age (PMA) of 35.5 ± 1.1 weeks. The range of plasma caffeine concentrations was 9.5-54.1 μg ml(-1) , with a mean difference (95% confidence interval) between plasma and salivary concentrations of -0.18 μg ml(-1) (-1.90, 1.54). Salivary and plasma caffeine concentrations were strongly correlated (Pearson's correlation coefficient = 0.87, P < 0.001). Caffeine PK in plasma and saliva was simultaneously described by a three-compartment recirculation model. Current body weight, birth weight, GA, PMA and postnatal age were not significantly correlated with any PK parameter.

CONCLUSIONS:

Salivary sampling provides an easy, non-invasive method for measuring caffeine concentrations. Salivary concentrations correlate highly with plasma concentrations. Caffeine PK in saliva and plasma are well described by a three-compartment recirculation model.

KEYWORDS:

caffeine; pharmacokinetic model; preterm infant; saliva

PMID:
27145974
PMCID:
PMC5338118
DOI:
10.1111/bcp.13001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center