Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Eur J Clin Pharmacol. 2011 Mar;67(3):261-6. doi: 10.1007/s00228-010-0928-9. Epub 2010 Nov 16.
It has been demonstrated that genetic variation in CYP2C19 has a significant influence upon H. pylori eradication rates. We have determined a dosage regimen of lansoprazole that will provide EMs with exposure approximately equivalent to that obtained by PMs treated with standard doses and determined the exposure that a PM would experience if they were to be treated with this 'EM optimised' lansoprazole dose.
Non-compartmental pharmacokinetic parameters (AUC, C(max), t(max)) for CYP2C19 genotypes were obtained from the literature. Primary pharmacokinetic parameters (CL, Vd, ka) for 200 virtual patients were calculated from the weighted non-compartmental variables and used to simulate a 7 day treatment course of twice daily lansoprazole, at standard and optimised doses for 1,000 patients.
The administration of 180 mg twice daily to CYP2C19 EMs results in approximately equivalent exposure to lansoprazole as the administration of standard 30 mg twice daily doses to PMs. Administration of this six-fold dose increase to EMs is predicted to result in only a 2.5-fold increase in C(max) when compared with PMs receiving the standard 30 mg dose.
We present a potential lansoprazole dosing regimen that should result in improved H. pylori eradication within CYP2C19 EMs and may not require individualization. Whilst the optimised dose represents a significant increase, it is below that reported in the chronic management of Zollinger-Ellison syndrome. On the basis that treatment is of limited duration and lansoprazole is generally well tolerated, such an approach warrants further in vivo evaluation to confirm drug exposure, efficacy and tolerability.
已经证明 CYP2C19 的遗传变异对幽门螺杆菌根除率有显著影响。我们确定了兰索拉唑的剂量方案，该方案将为 EM 提供与 PM 接受标准剂量治疗时获得的暴露量大致相当的暴露量，并确定 PM 如果接受这种“EM 优化”兰索拉唑剂量治疗，他们将经历的暴露量。
从文献中获得 CYP2C19 基因型的非房室药代动力学参数（AUC、C(max)、t(max)）。从加权非房室变量计算了 200 个虚拟患者的主要药代动力学参数（CL、Vd、ka），并用于模拟 7 天的兰索拉唑每日两次、标准剂量和优化剂量治疗 1000 名患者的疗程。
给予 CYP2C19 EM 每日两次 180mg，其兰索拉唑暴露量与给予 PM 标准剂量每日两次 30mg 相当。与接受标准 30mg 剂量的 PM 相比，给予 EM 这种六倍剂量增加预计只会使 C(max)增加 2.5 倍。
我们提出了一种潜在的兰索拉唑给药方案，这应该会提高 CYP2C19 EM 中的幽门螺杆菌根除率，并且可能不需要个体化治疗。虽然优化剂量代表了显著增加，但低于慢性管理 Zollinger-Ellison 综合征报道的剂量。鉴于治疗持续时间有限，并且兰索拉唑通常耐受性良好，因此这种方法值得进一步进行体内评估，以确认药物暴露量、疗效和耐受性。
