[Pharmacokinetics of theophylline and caffeine in premature infants with apnea (author's transl)].

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.