Reiter P D, Hogue S L, Phelps S J
University of Tennessee, Department of Clinical Pharmacy, Memphis 38103.
Ther Drug Monit. 1992 Oct;14(5):354-9. doi: 10.1097/00007691-199210000-00002.
The pharmacokinetic equations of Chiou, Koup, and Kurland are often used in the pediatric setting to predict steady-state theophylline clearance using non-steady serum theophylline concentrations. However, these equations have not been validated or compared in a pediatric population. We evaluated the ability of these equations to predict steady-state serum theophylline concentrations in 61 children (0.21-14.3 years) who received a continuous intravenous theophylline (0.79 +/- 0.12 mg/kg/h) infusion for a minimum of five half-lives. Theophylline concentrations used in the Kurland equation were obtained 10.8 +/- 4.5 h after initiation of therapy and the time between the two concentrations used in the Chiou and Koup equations was 9.2 +/- 3.9 h. Predicted steady-state theophylline concentration values for the three methods were not different from each other (p = 0.91), nor were they different from the observed steady-state concentration values (p = 0.92). The coefficient of determination for predicted vs. observed steady-state concentrations was statistically significant (p less than 0.001) and was comparable for the three methods. There was no difference in mean bias (p = 0.78), precision (p = 0.82), or % error (p = 0.86) values for the three methods. Regardless of the method used, 75 to 82% of all predicted theophylline concentrations were within 20% of the observed steady-state value. However, on average, all methods underpredicted the clearance and hence overpredicted the serum theophylline concentration. The Kurland method did not predict steady-state concentrations any better in patients who had received theophylline prior to admission.(ABSTRACT TRUNCATED AT 250 WORDS)
邱、库普和库兰德的药代动力学方程常用于儿科环境，通过非稳态血清茶碱浓度预测稳态茶碱清除率。然而，这些方程尚未在儿科人群中得到验证或比较。我们评估了这些方程预测61名儿童（0.21 - 14.3岁）稳态血清茶碱浓度的能力，这些儿童接受持续静脉输注茶碱（0.79±0.12mg/kg/h）至少五个半衰期。库兰德方程中使用的茶碱浓度在治疗开始后10.8±4.5小时获得，邱和库普方程中使用的两个浓度之间的时间间隔为9.2±3.9小时。三种方法预测的稳态茶碱浓度值彼此无差异（p = 0.91），与观察到的稳态浓度值也无差异（p = 0.92）。预测与观察到的稳态浓度的决定系数具有统计学意义（p＜0.001），且三种方法相当。三种方法的平均偏差（p = 0.78）、精密度（p = 0.82）或误差百分比（p = 0.86）值无差异。无论使用何种方法，所有预测的茶碱浓度中有75%至82%在观察到的稳态值的20%范围内。然而，平均而言，所有方法均低估了清除率，因此高估了血清茶碱浓度。库兰德方法在入院前接受过茶碱治疗的患者中预测稳态浓度并无更好表现。（摘要截断于250字）
