Cary J, Hein K, Dell R
Department of Pediatrics, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467-2490.
Ther Drug Monit. 1991 Jul;13(4):309-13. doi: 10.1097/00007691-199107000-00005.
Adolescents frequently require medication for acute and chronic illnesses. A proper dosage schedule is needed to achieve efficacy without toxicity during adolescence when there are marked changes in body size and organ function. Theophylline disposition was studied in 70 asthmatic adolescents, ages 8-18 years, to determine if pubertal changes in body size, composition, and organ function are associated with changes in drug disposition. Forty-eight youngsters were studied as outpatients and 22 while hospitalized. Half-life (t1/2) was computed for all patients. Volume of distribution and clearance were determined for inpatients only. Chronological age and anthropometric growth parameters were measured. Lean body mass (LBM) was derived from anthropometric measurements. Half-life was significantly correlated with developmental stage (Tanner r = 0.42, age r = 0.33, p less than 0.01), and body size (height r = 0.39, LBM r = 0.33, weight r = 0.33, p less than 0.01). LBM (kg/kg) was significantly correlated with volume of distribution (L/kg) (r = 0.59, p less than 0.01). Best-fits for t1/2 contained two variables: t1/2 = -4.57 + 1.31 (sex) + 0.0687 (height) (r = 0.48) and t1/2 = -3.54 + 1.32 (sex) + 0.0725 (LBM) (r = 0.43). Chronological age alone is not a useful basis for determining medication dosages due to the heterogeneity in rates of development and body size among adolescents. Half-life increases with increasing height or LBM. Although compliance is clearly an important factor in achieving optimal control of symptoms, this study demonstrates that dose adjustment during times of rapid growth during puberty is equally important.
青少年经常需要药物来治疗急慢性疾病。在青春期，身体大小和器官功能发生显著变化，因此需要适当的用药剂量方案，以在不产生毒性的情况下达到疗效。对70名8至18岁的哮喘青少年进行了茶碱处置研究，以确定青春期身体大小、组成和器官功能的变化是否与药物处置的变化相关。48名青少年作为门诊患者接受研究，22名在住院期间接受研究。计算了所有患者的半衰期（t1/2）。仅对住院患者测定了分布容积和清除率。测量了实际年龄和人体测量生长参数。瘦体重（LBM）通过人体测量得出。半衰期与发育阶段（坦纳分期r = 0.42，年龄r = 0.33，p < 0.01）和身体大小（身高r = 0.39，LBM r = 0.33，体重r = 0.33，p < 0.01）显著相关。LBM（kg/kg）与分布容积（L/kg）显著相关（r = 0.59，p < 0.01）。t1/2的最佳拟合包含两个变量：t1/2 = -4.57 + 1.31（性别）+ 0.0687（身高）（r = 0.48）和t1/2 = -3.54 + 1.32（性别）+ 0.0725（LBM）（r = 0.43）。由于青少年发育速度和身体大小存在异质性，仅实际年龄并不是确定药物剂量的有用依据。半衰期随身高或LBM的增加而增加。虽然依从性显然是实现症状最佳控制的重要因素，但本研究表明，青春期快速生长期间的剂量调整同样重要。
