Drug-Drug Interactions of P-gp Substrates Unrelated to CYP Metabolism
Autor: | Yumiko Akamine, Norio Yasui-Furukori, Tsukasa Uno |
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Rok vydání: | 2018 |
Předmět: |
Drug
Digoxin media_common.quotation_subject Clinical Biochemistry ATP-binding cassette transporter Pharmacology 030226 pharmacology & pharmacy Propanolamines 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Cytochrome P-450 Enzyme System medicine Animals Humans Drug Interactions ATP Binding Cassette Transporter Subfamily B Member 1 P-glycoprotein media_common Fexofenadine biology business.industry Transporter Dabigatran chemistry 030220 oncology & carcinogenesis biology.protein Terfenadine business medicine.drug Talinolol |
Zdroj: | Current drug metabolism. 20(2) |
ISSN: | 1875-5453 |
Popis: | Background:Recent US Food and Drug Administration (FDA) draft guidance on pharmacokinetic drugdrug interactions (DDIs) has highlighted the clinical importance of ABC transporters B1 or P-glycoprotein (P-gp), hepatic organic anion-transporting polypeptide transporters and breast cancer resistant protein because of their broad substrate specificity and the potential to be involved in DDIs. This guidance has indicated that digoxin, dabigatran etexilate and fexofenadine are P-gp substrate drugs and has defined P-gp inhibitors as those that increase the AUC of digoxin by ≧1.25-fold in clinical DDI studies. However, when substrate drugs of both CYPs and P-gp are involved in DDIs, it remains that the mechanisms of DDIs will be quite ambiguous in assessing how much the CYPs and/or drug transporters partially contribute to DDIs.Objective:Since there are no detailed manuscripts that summarizes P-gp interactions unrelated to CYP metabolism, this article reviews the effects of potent P-gp inhibitors and P-gp inducers on the pharmacokinetics of P-gp substrate drugs, including digoxin, talinolol, dabigatran etexilate, and fexofenadine in human studies. In addition, the present outcome were to determine the PK changes caused by DDIs among P-gp substrate drugs without CYP metabolism in human DDI studies.Conclusion:Our manuscript concludes that the PK changes of the DDIs among P-gp drugs unrelated to CYP metabolism are less likely to be serious, and it appears to be convincing that the absences of clinical effects caused to the PK changes by the P-gp inducers is predominant compared with the excessive effects caused to those by the P-gp inhibitors. |
Databáze: | OpenAIRE |
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