{"title":"[抗真菌药物和分子靶向药物之间的药物相互作用]。","authors":"Takeo Yamagiwa","doi":"10.11406/rinketsu.66.1215","DOIUrl":null,"url":null,"abstract":"<p><p>Drug interactions occur when the concomitant use of multiple drugs enhances or reduces their pharmacological effects, or causes unexpectedly strong adverse reactions. Major mechanisms include alterations in cytochrome P450 (CYP) enzyme activity, chelation within the gastrointestinal tract, and inhibition of renal transporters. In the treatment of hematologic malignancies, combination of molecular targeted therapies with immunosuppressants often increases the risk of infections due to drug-induced cytopenia and immunosuppression. Azole antifungal agents, frequently used for the prevention and treatment of fungal infections, are known to inhibit CYP enzymes. This inhibition can increase the plasma concentrations of targeted therapies, thereby enhancing their toxicity and increasing the risk of severe adverse effects. The degree of interaction is influenced not only by specific drug combinations but also by interindividual variability. Advanced pharmacokinetic approaches such as concentration ratio-interaction risk methods, physiologically based pharmacokinetic modeling, and population pharmacokinetic analysis allow for the prediction and evaluation of such interactions. These tools enable more precise drug selection and dosage adjustments tailored to individual patients, supporting treatment personalization and promoting safer, more effective drug therapy in clinical practice.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"66 9","pages":"1215-1221"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Drug-drug interactions between antifungal agents and molecular-targeted agents].\",\"authors\":\"Takeo Yamagiwa\",\"doi\":\"10.11406/rinketsu.66.1215\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Drug interactions occur when the concomitant use of multiple drugs enhances or reduces their pharmacological effects, or causes unexpectedly strong adverse reactions. Major mechanisms include alterations in cytochrome P450 (CYP) enzyme activity, chelation within the gastrointestinal tract, and inhibition of renal transporters. In the treatment of hematologic malignancies, combination of molecular targeted therapies with immunosuppressants often increases the risk of infections due to drug-induced cytopenia and immunosuppression. Azole antifungal agents, frequently used for the prevention and treatment of fungal infections, are known to inhibit CYP enzymes. This inhibition can increase the plasma concentrations of targeted therapies, thereby enhancing their toxicity and increasing the risk of severe adverse effects. The degree of interaction is influenced not only by specific drug combinations but also by interindividual variability. Advanced pharmacokinetic approaches such as concentration ratio-interaction risk methods, physiologically based pharmacokinetic modeling, and population pharmacokinetic analysis allow for the prediction and evaluation of such interactions. These tools enable more precise drug selection and dosage adjustments tailored to individual patients, supporting treatment personalization and promoting safer, more effective drug therapy in clinical practice.</p>\",\"PeriodicalId\":93844,\"journal\":{\"name\":\"[Rinsho ketsueki] The Japanese journal of clinical hematology\",\"volume\":\"66 9\",\"pages\":\"1215-1221\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"[Rinsho ketsueki] The Japanese journal of clinical hematology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.11406/rinketsu.66.1215\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"[Rinsho ketsueki] The Japanese journal of clinical hematology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.11406/rinketsu.66.1215","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
[Drug-drug interactions between antifungal agents and molecular-targeted agents].
Drug interactions occur when the concomitant use of multiple drugs enhances or reduces their pharmacological effects, or causes unexpectedly strong adverse reactions. Major mechanisms include alterations in cytochrome P450 (CYP) enzyme activity, chelation within the gastrointestinal tract, and inhibition of renal transporters. In the treatment of hematologic malignancies, combination of molecular targeted therapies with immunosuppressants often increases the risk of infections due to drug-induced cytopenia and immunosuppression. Azole antifungal agents, frequently used for the prevention and treatment of fungal infections, are known to inhibit CYP enzymes. This inhibition can increase the plasma concentrations of targeted therapies, thereby enhancing their toxicity and increasing the risk of severe adverse effects. The degree of interaction is influenced not only by specific drug combinations but also by interindividual variability. Advanced pharmacokinetic approaches such as concentration ratio-interaction risk methods, physiologically based pharmacokinetic modeling, and population pharmacokinetic analysis allow for the prediction and evaluation of such interactions. These tools enable more precise drug selection and dosage adjustments tailored to individual patients, supporting treatment personalization and promoting safer, more effective drug therapy in clinical practice.