Influence of Cytochrome P450 2C19 on the pharmacokinetics of lansoprazole administered by single and successive intravenous infusion in healthy Chinese volunteers


https://doi.org/10.4081/dts.2012.e3
Vol. 2 No. 1 (2012)
Submitted: 26 September 2011
Accepted: 12 December 2011
Published: 30 January 2012
CYP2C19 genotype, Extensive metabolizers (EMs), Lansoprazole, Poor metabolizers (PMs), proton-pump inhibitors (PPIs)
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Authors

  • Yongqing Wang
    wangyq999@yahoo.com.cn
    Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Peipei Zhang Department of Pharmacology, the China Pharmaceutical University, Nanjing, China.
  • Ningling Jiang Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Xiaojian Gong Department of Pharmacology, the China Pharmaceutical University, Nanjing, China.
  • Dewang Wang Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Nana Tang Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Hongwen Zhang Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Haibo Zhang Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Xiyong Zhang Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Ning Ou Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
  • Ling Meng Research Division of Clinical Pharmacology, Nanjing Medical University, Nanjing, China.
This study aimed to explore the effect of CYP2C19 polymorphisms on the pharmacokinetics of lansoprazole administered by single and successive intravenous (iv) infusions in healthy Chinese volunteers. A total of 30 subjects, including 20 extensive metabolizers (EMs) and 10 poor metabolizers (PMs) were recruited and randomly assigned to three groups receiving doses of 15, 30 and 60 mg. All subjects received a single dose of lansoprazole during a 60-min period, and only the 30 mg dose group continued to receive the same dose iv for the next seven days (twice daily). Plasma concentrations of lansoprazole were monitored by high performance liquid chromatography (HPLC) at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600 and 720 min after lansoprazole administration. After a single intravenous infusion in the three groups, AUC, Cmax and t½ were significantly higher in PMs than in EMs, while total clearance (Cltotal) in PMs was significantly lower than that in EMs. Mean AUC and Cmax ratios in EMs and PMs were 2.1:1 and 1.4:1, respectively. After repeated doses of 30 mg, the AUC, Cmax, and t½ increased significantly, while the Cltotal decreased significantly in EMs. Mean AUC and Cmax ratios in EMs and PMs amounted to 2.2:1.4 and 1.5:1.2, respectively. Lansoprazole displays a linear increase in AUC and Cmax over a dose range of 15-60 mg, and these were dependent on individual CYP2C19 status.

Supporting Agencies


Wang, Y., Zhang, P., Jiang, N., Gong, X., Wang, D., Tang, N., Zhang, H., Zhang, H., Zhang, X., Ou, N., & Meng, L. (2012). Influence of Cytochrome P450 2C19 on the pharmacokinetics of lansoprazole administered by single and successive intravenous infusion in healthy Chinese volunteers. Drugs and Therapy Studies, 2(1), e3. https://doi.org/10.4081/dts.2012.e3

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