ArticleActa pharmacologica Sinica2011
Effects of ticlopidine on pharmacokinetics of losartan and its main metabolite EXP-3174 in rats.
Article in Acta pharmacologica Sinica, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
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- Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch.Frontiers in pharmacology · 2021Article
- The Segregated Intestinal Flow Model (SFM) for Drug Absorption and Drug Metabolism: Implications on Intestinal and Liver Metabolism and Drug-Drug Interactions.Pharmaceutics · 2020Review
- Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism.Pharmaceutical biology · 2018Article
- Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC-MS/MS.Pharmaceutical biology · 2018Article
- The cytochrome P450 isoenzyme and some new opportunities for the prediction of negative drug interaction in vivo.Drug design, development and therapy · 2018Review
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Effect of Ginkgo Leaf Tablets on the Pharmacokinetics of Amlodipine in Rats.European journal of drug metabolism and pharmacokinetics · 2016Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimLosartan and antiplatelet agent ticlopidine can be prescribed concomitantly for prevention or therapy of cardiovascular diseases. Hence, the effects of ticlopidine on the pharmacokinetics of losartan and its active metabolite EXP-3174 were evaluated in rats.
methodsTiclopidine (4 or 10 mg/kg po) was administered 30 min before administration of losartan (9 mg/kg po or 3 mg/kg iv). The activity of human CYP2C9 and 3A4 were measured using the CYP inhibition assay kit. The activity of P-gp was evaluated using rhodamine-123 retention assay in MCF-7/ADR cells.
resultsTiclopidine (10 mg/kg) significantly increased the areas under the plasma concentration-time curves (AUCs) and peak plasma concentration (C(max)) of oral losartan (9 mg/kg), as well as the AUCs of the active metabolite EXP-3174. Ticlopidine (10 mg/kg) did not significantly change the pharmacokinetics of intravenous losartan (3 mg/kg). Ticlopidine inhibited CYP2C9 and 3A4 with IC₅₀ values of 26.0 and 32.3 μmol/L, respectively. The relative cellular uptake of rhodamine-123 was unchanged.
conclusionThe significant increase in the AUC of losartan (9 mg/kg) by ticlopidine (10 mg/kg) could be attributed to the inhibition of CYP2C9- and 3A4-mediated losartan metabolism in small intestine and/or in liver. The inhibition of P-gp in small intestine and reduction of renal elimination of losartan by ticlopidine are unlikely to be causal factors.
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