ArticleBritish journal of pharmacology2010
Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of metabolism of each drug by each other via hepatic and intestinal CYP3A1/2.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 47 citations in OpenAlex.
- Comparison of Metformin PBPK Models Incorporating Placental Transfer to Predict Fetal and Maternal Exposure.CPT: pharmacometrics & systems pharmacology · 2026Article
- The Impact of Hyperuricemia on Pharmacokinetics in Sprague-Dawley Rats.European journal of drug metabolism and pharmacokinetics · 2025Article
- A Fungistatic Strategy Using a Shear-Thinning pH-Responsive CMCS-OHA-Lp/Lr Hydrogel for Vulvovaginal Candidiasis.Pharmaceutics · 2025Article
- Mechanisms and effects of metformin on skeletal muscle disorders.Frontiers in neurology · 2023Review
- Meta-Assessment of Metformin Absorption and Disposition Pharmacokinetics in Nine Species.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Pharmacokinetic Drug Interaction between Tofacitinib and Voriconazole in Rats.Pharmaceutics · 2021Article
- Constitutive Androstane Receptor-Mediated Inhibition of Metformin on Phase II Metabolic Enzyme SULT2A1.International journal of endocrinology · 2021Article
- Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia.Frontiers in pharmacology · 2021Article
- Metformin disposition-A 40-year-old mystery.British journal of clinical pharmacology · 2020Article
- Interpretation of Drug Interaction Using Systemic and Local Tissue Exposure Changes.Pharmaceutics · 2020Review
- Physicochemical and pathohistological changes in experimental fibrosarcoma tumors of hamsters treated with metformin and itraconazole.Oncology letters · 2019Article
- Use of bedaquiline and delamanid in diabetes patients: clinical and pharmacological considerations.Drug design, development and therapy · 2016Review
- Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats.Pharmacognosy magazine · 2015Article
- Determination of drug toxicity using 3D spheroids constructed from an immortal human hepatocyte cell line.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene.Biochemical pharmacology · 2011Article
- Characterization of the inhibitory effects of N-butylpyridinium chloride and structurally related ionic liquids on organic cation transporters 1/2 and human toxic extrusion transporters 1/2-k in vitro and in vivo.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Sustained drug-delivery system: a promising therapy for denture stomatitis?Journal of applied oral science : revista FOBArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeFungal infection is prevalent in patients with diabetes mellitus. Thus, we investigated whether a pharmacokinetic interaction occurs between the anti-fungal agent itraconazole and the anti-glycaemic drug metformin, as both drugs are commonly administered together to diabetic patients and are metabolized via hepatic CYP3A subfamily in rats. EXPERIMENTAL APPROACH: Itraconazole (20 mg·kg(-1)) and metformin (100 mg·kg(-1)) were simultaneously administered i.v. and p.o. to rats. Concentrations (I) of each drug in the liver and intestine, maximum velocity (V(max)), Michaelis-Menten constant (K(m)) and intrinsic clearance (CL(int) ) for the disappearance of each drug, apparent inhibition constant (K(i) ) and [I]/K(i) ratios of each drug in the liver and intestine were determined. Also the metabolism of each drug in rat and human CYPs was measured in vitro. KEY
resultsAfter simultaneous administration of both drugs, either i.v. or p.o., the total area under the plasma concentration-time curve from time zero to infinity (AUC)s of itraconazole and metformin were significantly greater than that of either drug administered alone. The metabolism of itraconazole and metformin was significantly inhibited by each other via CYP3A1 and 3A2 in rat and 3A4 in human microsomes. CONCLUSIONS AND IMPLICATIONS: The significantly greater AUCs of itraconazole and metformin after i.v. administration of both drugs are probably due to competitive inhibition of the metabolism of each drug by each other via hepatic CYP3A1/2. Whereas after oral administration of both drugs, the significantly greater AUCs of each drug administered together than that of either drug alone is mainly due to competitive inhibition of intestinal metabolism of each drug by each other via intestinal CYP3A1/2.
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