ArticleBMC pharmacology & toxicology2026
Effects of CYP1A2 genetic polymorphisms on the pharmacokinetics of pentoxifylline and its active metabolites.
Article in BMC pharmacology & toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTo investigate whether the CYP1A2 genetic polymorphisms could affect the pharmacokinetics of pentoxifylline and its two active metabolites in Chinese healthy participants.
methodsForty-six healthy Chinese volunteers were administered a single 400 mg oral dose of pentoxifylline. The plasma concentrations of pentoxifylline and its active metabolites were quantified using LC-MS/MS. The CYP1A2 genotypes for the following loci were determined by the SnapShot technique: -5347T > C (rs2470890), -3860G > A (rs2069514), -3594T > G (rs2069520), -3113 C > A (rs2069521), -2467delT (rs35694136), -739T > G (rs2069526), -163 C > A (rs762551), and 2159G > A (rs2472304).
resultsParticipants heterozygous for the CYP1A2 -3860G/A genotype exhibited a 22.3% and 17.6% reduction in the Cmax of metabolite M5 compared to homozygous − 3860G/G and − 3860 A/A carriers, respectively. Participants carrying the CYP1A2 -3860G/A genotype exhibited reduced AUC0–t and AUC0–∞ values of metabolite M5 compared to both homozygous − 3860G/G and − 3860 A/A carriers. Additionally, participants with the CYP1A2 -163 C/A genotype had significantly lower pentoxifylline AUC0–t and AUC0–∞ than those with the − 163 C/C genotype (reduced by 29.14% and 28.62%, respectively). In contrast, no significant differences were observed in the pharmacokinetic parameters of the primary metabolites M1 and M5 across the different CYP1A2 genotype groups.
conclusionsThe two CYP1A2 polymorphisms significantly affected pharmacokinetics: the − 3860G > A variant was associated with a significant reduction in systemic exposure to metabolite M5, while potentially increasing exposure to pentoxifylline and M1. Conversely, the − 163 C > A variant significantly reduced the plasma exposure of the parent drug pentoxifylline, with a trend toward decreased exposure for metabolites M1 and M5.
trial registrationThis clinical trial has been registered in the Chinese Clinical Trial Register (accessible at http://www.chinadrugtrials.org.cn/index.htmL ) with the registration number CTR20233180 on October 08, 2023.
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