Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters
| Autor: | F. P. Guengerich, Slobodan Rendic |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
media_common.quotation_subject Clinical Biochemistry Pharmacology 030226 pharmacology & pharmacy Article 03 medical and health sciences 0302 clinical medicine Cytochrome P-450 Enzyme System In vivo Chloroquine Animals Cytochrome P-450 Enzyme Inhibitors Humans Medicine Drug Interactions ADME media_common chemistry.chemical_classification biology business.industry COVID-19 Membrane Transport Proteins Cytochrome P450 Hydroxychloroquine COVID-19 Drug Treatment Enzyme Pharmaceutical Preparations chemistry 030220 oncology & carcinogenesis biology.protein business medicine.drug |
| Zdroj: | Curr Drug Metab |
| ISSN: | 1389-2002 |
| DOI: | 10.2174/1389200221999201208211537 |
| Popis: | Background:: In clinical practice, chloroquine and hydroxychloroquine are often co-administered with other drugs in the treatment of malaria, chronic inflammatory diseases, and COVID-19. Therefore, their metabolic properties and the effects on the activity of cytochrome P450 (P450, CYP) enzymes and drug transporters should be considered when developing the most efficient treatments for patients. Methods:: Scientific literature on the interactions of chloroquine and hydroxychloroquine with human P450 enzymes and drug transporters, was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/) and the ADME database (https://life-science.kyushu.fujitsu.com/admedb/). Results:: Chloroquine and hydroxychloroquine are metabolized by P450 1A2, 2C8, 2C19, 2D6, and 3A4/5 in vitro and by P450s 2C8 and 3A4/5 in vivo by N-deethylation. Chloroquine effectively inhibited P450 2D6 in vitro; however, in vivo inhibition was not apparent except in individuals with limited P450 2D6 activity. Chloroquine is both an inhibitor and inducer of the transporter MRP1 and is also a substrate of the Mate and MRP1 transport systems. Hydroxychloroquine also inhibited P450 2D6 and the transporter OATP1A2. Conclusions:: Chloroquine caused a statistically significant decrease in P450 2D6 activity in vitro and in vivo, also inhibiting its own metabolism by the enzyme. The inhibition indicates a potential for clinical drug-drug interactions when taken with other drugs that are predominant substrates of the P450 2D6. When chloroquine and hydroxychloroquine are used clinically with other drugs, substrates of P450 2D6 enzyme, attention should be given to substrate-specific metabolism by P450 2D6 alleles present in individuals taking the drugs. |
| Databáze: | OpenAIRE |
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