title: Salivary caffeine concentrations are comparable to plasma concentrations in preterm infants receiving extended caffeine therapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Pediatrics, Tripler Army Medical Center, Honolulu, HI, USA.|Pediatrics, Uniformed Services University, Bethesda, MD, USA.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Dobson
authors.affiliation: Clinical Pharmacology, Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Newborn Medicine and Respiratory Diseases, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Rhein
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Darnall
authors.affiliation: Slone Epidemiology Center, Boston University, Boston, MA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Corwin
authors.affiliation: American SIDS Institute, Naples, FL, USA.
authors.forename: Betty L
authors.initials: BL
authors.lastname: McEntire
authors.affiliation: Clinical Pharmacology, Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Ward
authors.affiliation: Pediatrics, University of Arkansas, Little Rock, AR, USA.
authors.forename: Laura P
authors.initials: LP
authors.lastname: James
authors.affiliation: Clinical Pharmacology, Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.affiliation: Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Heeren
authors.affiliation: Pediatrics, Uniformed Services University, Bethesda, MD, USA.|Pediatrics, George Washington University, Washington, DC, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Hunt
mesh_terms: D002110:Caffeine / Q000032:analysis* / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D008954:Models, Biological; D012463:Saliva / Q000737:chemistry*
chemical_list: D002110:Caffeine
keywords: caffeine; pharmacokinetic model; preterm infant; saliva