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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. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure ( PAE) increases the risk for The Sudden Infant Death Syndrome ( SIDS) in human infants. In rat pups, the arousal response to hypoxia is modulated by medullary raphe GABAergic mechanisms. We hypothesized that arousal to hypoxia is impaired by PAE, and is associated with an increase in medullary GABA and enhanced GABAergic activity. Pregnant dams received an ethanol liquid diet ( ETOH), an iso-caloric pair fed diet ( PF) or a standard chow diet ( CHOW). We first measured the time to arousal (latency), during four episodes of hypoxia in P5, P15, and P21 CHOW, PF, and ETOH pups. We also measured brainstem GABA concentration in the same groups of pups. Finally, we injected artificial cerebrospinal fluid ( aCSF), nipecotic acid ( NIP) or gabazine into the medullary raphe of P15 and P21 pups receiving the three diets. For statistical analysis, the PF and CHOW groups were combined into a single CONTROL group. Our main finding was that compared to CONTROL, arousal latency to hypoxia is increased in ETOH pups at P15 and P21, and the concentration of brainstem GABA is elevated at P21. NIP administration in CONTROL pups led to arousal latencies similar in magnitude to those in ETOH pups after aCSF injection. NIP injected ETOH pups had no further increases in arousal latency. We conclude that PAE impairs arousal latency and this is mediated or modulated by medullary GABAergic mechanisms. [ABSTRACT FROM AUTHOR]

We evaluated the hypothesis that a 'central oxygen detector' in the brainstem is necessary for depressions of ventilatory activity to be manifested in the newborn. Decerebrate piglets, ventilated with 100 % O(2), were studied following neuromuscular blockade. The vagi and carotid sinus nerves were sectioned bilaterally in order to remove the influence of the peripheral chemoreceptors. Activity of the phrenic nerve was recorded as the index of the central respiratory rhythm. This activity declined and, in some preparations, ceased upon ventilation with air or a hypoxic gas, at either normocapnia or hypercapnia. The degree of depression in hypercapnic hypoxia was greatest in the youngest piglets. Following a medial section of the brainstem, extending to the caudal pons, the depression was reduced. In some preparations, a similar reduction followed the placement of radiofrequency lesions in the caudal ventromedial pons. We conclude that a region of the caudal mesencephalon or pons is necessary for the manifestation of depressions of ventilatory activity in the newborn pig.