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Purpose <p>The objective of this study was to evaluate the influence of genetic polymorphisms in drug transporters on the pharmacokinetics of pentoxifylline (PTX) and its key active metabolites in a healthy Chinese population.</p> Subjects and methods <p> Forty-six healthy Chinese volunteers were enrolled and took oral administration of 400 mg pentoxifylline. Plasma concentrations of PTX and its active metabolites (M1 and M5) were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Genotyping of ABCB1 (3435C&gt;T, 1236C&gt;T, 2677G&gt;T/A), ABCG2 (421C&gt;A, 34G&gt;A), and ABCC2 (-24C&gt;T, 1249G&gt;A, 3972C&gt;T) was performed using the SnapShot technique.</p> Results <p> Under fasting conditions, subjects carrying the ABCB1 3435C/T genotype demonstrated a significantly lower AUC (P &lt; 0.05, Bonferroni-corrected) and a higher CL/F (P &lt; 0.01, Bonferroni-corrected) of PTX compared to those carrying the ABCB1 3435C/C genotype. Furthermore, carriers of the ABCB1 3435C/T genotype exhibited a significantly higher metabolic conversion rate to M5 (P &lt; 0.05, Bonferroni-corrected). Similarly, subjects with the ABCB1 2677(A/A+A/T) genotypes also showed a higher M5 conversion rate (P &lt; 0.05, Bonferroni-corrected).</p> Conclusion <p> The ABCB1 3435C&gt;T and 2677G&gt;T/A polymorphisms are associated with variations in the pharmacokinetics of PTX and its active metabolites.</p>

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Effects of ABC transporter polymorphism on the pharmacokinetics of pentoxifylline and its active metabolites in healthy Chinese subjects

  • 期刊论文

  • 发表日期：

    2026年1月19日

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  • Lingfang Guo,
  • Xue Sun,
  • Bo Qiu,
  • Wanjun Bai,
  • Yabin Du,
  • Haojing Song

摘要

Purpose

The objective of this study was to evaluate the influence of genetic polymorphisms in drug transporters on the pharmacokinetics of pentoxifylline (PTX) and its key active metabolites in a healthy Chinese population.

Subjects and methods

Forty-six healthy Chinese volunteers were enrolled and took oral administration of 400 mg pentoxifylline. Plasma concentrations of PTX and its active metabolites (M1 and M5) were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Genotyping of ABCB1 (3435C>T, 1236C>T, 2677G>T/A), ABCG2 (421C>A, 34G>A), and ABCC2 (-24C>T, 1249G>A, 3972C>T) was performed using the SnapShot technique.

Results

Under fasting conditions, subjects carrying the ABCB1 3435C/T genotype demonstrated a significantly lower AUC (P < 0.05, Bonferroni-corrected) and a higher CL/F (P < 0.01, Bonferroni-corrected) of PTX compared to those carrying the ABCB1 3435C/C genotype. Furthermore, carriers of the ABCB1 3435C/T genotype exhibited a significantly higher metabolic conversion rate to M5 (P < 0.05, Bonferroni-corrected). Similarly, subjects with the ABCB1 2677(A/A+A/T) genotypes also showed a higher M5 conversion rate (P < 0.05, Bonferroni-corrected).

Conclusion

The ABCB1 3435C>T and 2677G>T/A polymorphisms are associated with variations in the pharmacokinetics of PTX and its active metabolites.