儿童口服兰索拉唑的药代动力学-药效学研究

Pharmacokinetic-pharmacodynamic study of oral lansoprazole in children.

作者信息

Tran Agnès, Rey Elisabeth, Pons Gérard, Pariente-Khayat Ann, D'Athis Philippe, Sallerin Valentine, Dupont Christophe

机构信息

Pharmacologie Périnatale et Pédiatrique, Gastroentérologie Pédiatrique, Université René Descartes, Hôpital Saint-Vincent de Paul, 82 Avenue Denfert-Rochereau, Assistance Publique-Hôpitaux de Paris, 75674 Paris, France.

出版信息

Clin Pharmacol Ther. 2002 May;71(5):359-67. doi: 10.1067/mcp.2002.122472.

DOI:10.1067/mcp.2002.122472

PMID:12011821

Abstract

OBJECTIVE

We investigated the pharmacokinetics, pharmacodynamics, and tolerability of lansoprazole in children after single and multiple administrations.

METHODS

Forty children (age range, 18 days-14 years) with gastric acid-related disorders entered an open study and received lansoprazole in a single dose of 17 mg. m(-2) (group A) or in multiple doses (17 mg. m(-2) per day) for 7 to 14 days (group B). Lansoprazole plasma concentrations were measured by HPLC. A 24-hour intragastric pH monitoring assessed the antisecretory effect.

RESULTS

In group A, maximal concentration (C(max)) was 1023 +/- 775 (mg. L(-1))/(17 mg. m(-2)), time to reach C(max) was 1.8 +/- 0.8 hours, elimination half-life was 1.5 +/- 2.0 hours, area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] was 3503 +/- 6025 (mg. L(-1). h)/(17 mg. m(-2)), apparent plasma clearance was 0.57 +/- 0.47 L. h(-1). kg(-1), and apparent volume of distribution was 0.61 +/- 0.36 L. kg(-1). In group B, C(max) was 750 +/- 511 (mg. L(-1))/(17 mg. m(-2)), time to reach C(max) was 1.8 +/- 1.1 hours, elimination half-life was 1.2 +/- 1.1 hours, AUC(0-infinity) was 2351 +/- 3691 (mg. L(-1). h)/(17 mg. m(-2)), apparent plasma clearance was 0.71 +/- 0.50 L. h(-1). kg(-1), and apparent volume of distribution was 0.9 +/- 0.7 L. kg(-1). No influence of age was shown on pharmacokinetic parameters in both groups. However, data suggested that elimination was reduced in neonates and higher in infants than in adults. The values for 24-hour percentage of time at gastric pH <4 and pH <3 were 61% +/- 21% and 51% +/- 21% (group A) and 47% +/- 24% and 37% +/- 21% (group B), respectively. In both groups the antisecretory effect decreased with age, and in group A it was positively correlated to C(max) and AUC(0-infinity). The mean gastrin serum concentration significantly increased (+31%) after 12.6 +/- 1.5 days of treatment.

CONCLUSIONS

Lansoprazole was well tolerated in children. After a single oral dose of 30 mg per 1.73 m(2), there was a trend for the elimination to be higher in infants than in adults and the antisecretory effect appeared to be higher in infants younger than 6 months than in older children and adults.

摘要

目的

我们研究了单次及多次给药后兰索拉唑在儿童体内的药代动力学、药效学及耐受性。

方法

40名患有胃酸相关疾病的儿童（年龄范围为18天至14岁）进入一项开放性研究，接受单剂量17mg·m⁻²的兰索拉唑（A组）或多剂量（每天17mg·m⁻²）给药7至14天（B组）。通过高效液相色谱法测定兰索拉唑血浆浓度。采用24小时胃内pH监测评估抑酸效果。

结果

A组中，最大浓度（C(max)）为1023±775（mg·L⁻¹）/（17mg·m⁻²），达到C(max)的时间为1.8±0.8小时，消除半衰期为1.5±2.0小时，从零时间至无穷大的浓度 - 时间曲线下面积[AUC(0 - ∞)]为3503±6025（mg·L⁻¹·h）/（17mg·m⁻²），表观血浆清除率为0.57±0.47L·h⁻¹·kg⁻¹，表观分布容积为0.61±0.36L·kg⁻¹。B组中，C(max)为750±511（mg·L⁻¹）/（17mg·m⁻²），达到C(max)的时间为1.8±1.1小时，消除半衰期为1.2±1.1小时，AUC(0 - ∞)为2351±3691（mg·L⁻¹·h）/（17mg·m⁻²），表观血浆清除率为0.71±0.50L·h⁻¹·kg⁻¹，表观分布容积为0.9±0.7L·kg⁻¹。两组中均未显示年龄对药代动力学参数有影响。然而，数据表明新生儿的消除率降低，婴儿的消除率高于成人。胃内pH<4和pH<3的24小时时间百分比值在A组分别为61%±21%和51%±21%，在B组分别为47%±24%和37%±21%。两组中抑酸效果均随年龄降低，且在A组中与C(max)和AUC(0 - ∞)呈正相关。治疗12.6±1.5天后，血清胃泌素平均浓度显著升高（+31%）。