Emma Children's Hospital/Academic Medical Centre, Amsterdam, The NetherlandsDepartment of Clinical Pharmacology and Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Clin Drug Investig. 2004;24(2):113-20. doi: 10.2165/00044011-200424020-00006.
To determine pharmacokinetic data for pravastatin in children, since current data are insufficient in this age group.
A 2-week, multiple-dose, steady-state pharmacokinetic study was carried out with pravastatin 20mg daily in 24 children with familial hypercholesterolaemia (aged 8-16 years; 12 prepubertal, 12 pubertal). A plasma concentration-time curve was performed on day 14. Pharmacokinetic curves for each individual were constructed using nonparametric methods, yielding area under the plasma concentration-time curve (AUC), maximum plasma concentration (C(max)) and half-life (t((1/2))). Clearance values and volumes of distribution were calculated from these parameters. Cholesterol lowering was observed on day 14 and 6 weeks after the start of pravastatin.
The C(max) in prepubertal (group A) children (52.1 +/- 27.0 mug/L [mean +/- SD]) differed, although not significantly (p = 0.09, unpaired two-tailed t-test), from the C(max) in adolescents (group B) [31.7 +/- 29.2 mug/L]. There was a moderate negative correlation between C(max) and age (Spearman correlation r = -0.42; p = 0.04). The AUC in prepubertal children (91.3 +/- 39.7 mug . h/L) did not differ significantly from the AUC in adolescents (69.3 +/- 57.0 mug . h/L). The t((1/2)) was the same for the two groups: 2.5 +/- 1.1h. Clearance values (CL/f) varied widely between the two groups (group A: 4.3 +/- 1.8 L/min; group B: 11.0 +/- 11.9 L/min; p = 0.08). A moderate positive correlation was found between clearance and age (Spearman correlation r = 0.36; p = 0.09). A large variation was found in the volumes of distribution within the two groups (group A: 31.2 mL/kg [SD 26.7], group B:37.0 mL/kg [SD 29.6]; p = 0.12). A very weak positive correlation was found between age and volume of distribution (Spearman correlation r = 0.11; p = 0.61). A 27% low-density lipoprotein-cholesterol reduction from baseline was achieved at day 14.
Body surface area and gender did not influence the pharmacokinetics of pravastatin in children aged 8-16 years. On the basis of our findings there are no reasons to use pravastatin at a dosage according to bodyweight or to use different dosage regimens from those in adults. However, for prepubertal children half the advised starting dose for adults may be sufficient.
确定普伐他汀在儿童中的药代动力学数据，因为目前在该年龄组的数据不足。
对 24 例家族性高胆固醇血症儿童（年龄 8-16 岁；12 例青春期前，12 例青春期）进行为期 2 周的、多剂量、稳态药代动力学研究。在第 14 天进行血浆浓度-时间曲线。使用非参数方法为每个个体构建药代动力学曲线，得到血浆浓度-时间曲线下面积（AUC）、最大血浆浓度（C（max））和半衰期（t（1/2））。从这些参数计算清除率值和分布容积。在开始使用普伐他汀后第 14 天和 6 周观察到降胆固醇作用。
青春期前儿童（A 组）的 C（max）（52.1 +/- 27.0 mug/L [平均值 +/- SD]）与青春期儿童（B 组）的 C（max）[31.7 +/- 29.2 mug/L]不同，但差异无统计学意义（p = 0.09，未配对双侧 t 检验）。C（max）与年龄之间存在中度负相关（Spearman 相关 r = -0.42；p = 0.04）。青春期前儿童的 AUC（91.3 +/- 39.7 mug. h/L）与青春期儿童的 AUC（69.3 +/- 57.0 mug. h/L）无显著差异。两组的 t（1/2）相同：2.5 +/- 1.1 h。两组间清除率值（CL/f）差异很大（A 组：4.3 +/- 1.8 L/min；B 组：11.0 +/- 11.9 L/min；p = 0.08）。发现清除率与年龄之间存在中度正相关（Spearman 相关 r = 0.36；p = 0.09）。两组的分布容积差异很大（A 组：31.2 mL/kg [SD 26.7]，B 组：37.0 mL/kg [SD 29.6]；p = 0.12）。年龄与分布容积之间存在非常弱的正相关（Spearman 相关 r = 0.11；p = 0.61）。第 14 天从基线降低了 27%的低密度脂蛋白胆固醇。
在 8-16 岁的儿童中，体表面积和性别不影响普伐他汀的药代动力学。根据我们的发现，没有理由根据体重使用普伐他汀或使用与成人不同的剂量方案。然而，对于青春期前儿童，成人建议起始剂量的一半可能就足够了。
