| Sumario: | 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.
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