Pons G, Carrier O, Richard M O, Rey E, d'Athis P, Moran C, Badoual J, Olive G
Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, Université René Descartes, Paris, France.
Dev Pharmacol Ther. 1988;11(5):258-64. doi: 10.1159/000457700.
Five neonates (4 premature) and 16 infants (6 prematurely born), 15-588 days old, received caffeine as citrate salt for apnea. Plasma samples were collected 0, 2, 4, 6 h after a dose and before the next scheduled one. Patients 8 and 9 were serially studied. Caffeine plasma concentrations were determined using HPLC. The caffeine elimination half-life and clearance varied linearly with gestational age and exponentially with postnatal age, the plateau being reached during the second trimester of life. Dose regimen guidelines as a function of postnatal age were derived from individually calculated doses and dosing intervals in order to achieve, at steady state, a caffeine mean plasma concentration of 11 mg/l with a minimum of 7.5 mg/l and a maximum of 14.5 mg/l. We suggest dosing intervals for infants before 1 month, 1-2 months, 2-4 months and after 4 months to be equal to 24, 12, 8 and 6 h, respectively. The individual recommended dose varies from 2 to 10 mg/kg (as caffeine base) making caffeine monitoring mandatory in infants.
5名新生儿（4名早产儿）和16名婴儿（6名早产儿），年龄在15至588天之间，因呼吸暂停接受枸橼酸盐咖啡因治疗。在给药后0、2、4、6小时以及下次预定给药前采集血样。对患者8和患者9进行了连续研究。使用高效液相色谱法测定咖啡因血浆浓度。咖啡因的消除半衰期和清除率与胎龄呈线性关系，与出生后年龄呈指数关系，在生命的第二个月达到平稳状态。根据出生后年龄制定的给药方案指南源自个体计算的剂量和给药间隔，以便在稳态时使咖啡因平均血浆浓度达到11毫克/升，最低为7.5毫克/升，最高为14.5毫克/升。我们建议1个月龄前、1至2个月龄、2至4个月龄以及4个月龄后的婴儿给药间隔分别为24、12、8和6小时。个体推荐剂量为2至10毫克/千克（以咖啡因碱计），这使得对婴儿进行咖啡因监测成为必要。
