Riechert M, Lipowsky G, Stöckl H, Stiegler H
Monatsschr Kinderheilkd. 1981 Dec;129(12):697-702.
In apneic premature infants treated with theophylline or caffeine the pharmacokinetics of the methylxanthines were investigated. Orally applied caffeine and theophylline were rapidly absorbed reaching peak plasma levels at 1-2 and 1-4 h resp. The plasma concentration of free theophylline was significantly higher (p less than 0.001) in prematures than in adults. In prematures and adults only 5 resp. 8% of caffeine were bound to the plasma proteins. The salivary methylxanthine concentration corresponds to the plasma concentration of the free drugs. The mean plasma half-live of theophylline was 22.3 h, the clearance 28.3 ml/kg/h and the volume of distribution 0.9 l/kg. For caffeine a plasma half-live of 70.6 h, a clearance of 8.6 ml/h/kg and a volume of distribution of 0.84 l/kg was found. A first oral dose of 7-9 mg/kg theophylline or caffeine should be administered to reach rapidly effective plasma concentrations of about 10 micrograms/ml. To maintain a mean plasma concentration of about 10 micrograms/ml, a daily oral maintenance dose of 5-9 mg/kg theophylline or 2 mg/kg caffeine should be given. High concentrations of unchanged caffeine and theophylline were excreted in the urine of premature infants indicating immaturity of the metabolizing hepatic enzymes. In prematures treated with theophylline caffeine was found in plasma as a metabolite of theophylline.
对接受茶碱或咖啡因治疗的呼吸暂停早产儿的甲基黄嘌呤类药物的药代动力学进行了研究。口服给予的咖啡因和茶碱吸收迅速，分别在1 - 2小时和1 - 4小时达到血浆峰值水平。早产儿游离茶碱的血浆浓度显著高于成年人（p < 0.001）。在早产儿和成年人中，分别只有5%和8%的咖啡因与血浆蛋白结合。唾液中甲基黄嘌呤的浓度与游离药物的血浆浓度相对应。茶碱的平均血浆半衰期为22.3小时，清除率为28.3毫升/千克/小时，分布容积为0.9升/千克。对于咖啡因，发现其血浆半衰期为70.6小时，清除率为8.6毫升/小时/千克，分布容积为0.84升/千克。应给予7 - 9毫克/千克的茶碱或咖啡因首剂口服，以迅速达到约10微克/毫升的有效血浆浓度。为维持约10微克/毫升的平均血浆浓度，应给予5 - 9毫克/千克的茶碱每日口服维持剂量或2毫克/千克的咖啡因。高浓度的未代谢咖啡因和茶碱在早产儿尿液中排泄，表明肝脏代谢酶不成熟。在接受茶碱治疗的早产儿血浆中发现咖啡因是茶碱的代谢产物。
