Nicole R Dobson1,2, Xiaoxi Liu3, Lawrence M Rhein4, Robert A Darnall5, Michael J Corwin6, Betty L McEntire7, Robert M Ward3, Laura P James8, Catherine M T Sherwin3, Timothy C Heeren9, Carl E Hunt2,10. 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.
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.
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