Lee T C, Charles B G, Steer P A, Flenady V J
Department of Pharmacy, University of Queensland, Brisbane, Australia.
Ther Drug Monit. 1996 Jun;18(3):288-93. doi: 10.1097/00007691-199606000-00012.
Caffeine is a potentially useful alternative to theophylline for the treatment and prevention of apnea of prematurity because of its lower toxicity and longer terminal half-life. Monitoring of salivary caffeine concentrations is less invasive than blood sampling, especially in very sick premature neonates. Caffeine citrate-3 mg/kg, 15 mg/kg, or 30 mg/kg-was administered once daily for 7 days in a randomized, parallel design to 59 newborn, premature infants with an initial loading dose of twice the maintenance dose. Serum and saliva samples (131 pairs) were collected and assayed by high-performance liquid chromatography (HPLC) for caffeine content. Measurable caffeine concentrations in serum ranged from 0.28 to 93.3 mg/L and in saliva from 0.35 to 91.5 mg/L. The mean ratio of the saliva-to-serum concentrations was 0.924. There was no significant difference in precision between the serum and salivary data. The mean serum caffeine concentration was 29.9 mg/L, and the mean salivary concentration was 27.7 mg/L, indicating a small negative bias for saliva versus serum monitoring. Salivary caffeine concentration monitoring is a satisfactory alternative to blood sampling across a wide range of caffeine doses used to treat apnea.
由于咖啡因毒性较低且终末半衰期较长，它是治疗和预防早产儿呼吸暂停的一种潜在有用的替代茶碱的药物。监测唾液中咖啡因浓度的侵入性低于采血，尤其是对于病情非常严重的早产新生儿。采用随机平行设计，对59例早产新生儿每日一次给予柠檬酸咖啡因，剂量分别为3mg/kg、15mg/kg或30mg/kg，持续7天，初始负荷剂量为维持剂量的两倍。采集血清和唾液样本（131对），采用高效液相色谱法（HPLC）测定咖啡因含量。血清中可测量的咖啡因浓度范围为0.28至93.3mg/L，唾液中为0.35至91.5mg/L。唾液与血清浓度的平均比值为0.924。血清和唾液数据的精密度无显著差异。血清咖啡因平均浓度为29.9mg/L，唾液平均浓度为27.7mg/L，表明唾液监测相对于血清监测存在较小的负偏差。在用于治疗呼吸暂停的广泛咖啡因剂量范围内，唾液咖啡因浓度监测是一种令人满意的替代采血的方法。
