Evaluation of the Effects of Maytenus ilicifolia on the Activities of Cytochrome P450 3A and P-glycoprotein
| Autor: | Laís Lobato de Araújo, Isabela Costa César, Joaquim Maurício Duarte-Almeida, Hartmut Derendorf, Mariana de Lima Nascimento, Whocely Victor de Castro, Flávio Martins de Oliveira, João Máximo de Siqueira, Sara Batista do Nascimento, Maria do Carmo Vieira |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
CYP3A Midazolam Clinical Biochemistry Cmax Pharmacology Cell Line Pharmacokinetics medicine Animals Cytochrome P-450 CYP3A Humans Drug Interactions ATP Binding Cassette Transporter Subfamily B Member 1 Rats Wistar P-glycoprotein Fexofenadine biology Plant Extracts Chemistry Maytenus Rats Ketoconazole Polyphenol Toxicity Quinolines biology.protein Cytochrome P-450 CYP3A Inhibitors Terfenadine Caco-2 Cells medicine.drug |
| Zdroj: | Current Drug Metabolism. 21:281-290 |
| ISSN: | 1389-2002 |
| DOI: | 10.2174/1389200221666200512112718 |
| Popis: | Background: Maytenus ilicifolia is a Brazilian popular medicine commonly used to treat ulcer and gastritis. Despite the absence of toxicity regarding its consumption, possible interactions when co-administrated with conventional drugs, are unknown. Objective: This study aimed to evaluate the effects of M. ilicifolia extracts on Cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) activities. Method: The extracts were obtained by infusion (MI) or turbo-extraction using hydro-acetonic solvent (MT70). The content of polyphenols in each extract was determined. To assess the modulation of M. ilicifolia on P-gp activity, the uptake of fexofenadine (FEX) by Caco-2 cells was investigated in the absence or presence of MI or MT70. The effect on CYP3A activity was evaluated by the co-administration of midazolam (MDZ) with each extract in male Wistar rats. The pharmacokinetic parameters of the drug were determined and compared with those from the control group. The content of total phenolic compounds, tannins, and flavonoids on MT70 extract was about double of that found in MI. Results: In the presence of the extracts, the uptake of the P-gp marker (FEX) by Caco-2 cells increased from 1.7 ± 0.4 ng.mg-1 protein (control) to 3.5 ± 0.2 ng.mg-1 protein (MI) and 4.4 ± 0.5 ng.mg-1 protein (MT70), respectively. When orally co-administrated with MDZ (substrate of CYP3A), the extracts augmented the AUC(0-∞) (Control: 911.7 ± 215.7 ng.h.mL-1; MI: 1947 ± 554.3 ng.h.mL-1; MT70: 2219.0 ± 506.3 ng.h.mL-1) and the Cmax (Control: 407.7 ± 90.4 ng.mL-1; MI: 1770.5 ± 764.5 ng.mL-1; MT70: 1987.2 ± 544.9 ng.mL-1) of the drug in rats indicating a 50% reduction of the oral Cl. No effect was observed when midazolam was given intravenously. Conclusion: The results suggest that M. ilicifolia can inhibit the intestinal metabolism and transport of drugs mediated by CYP3A and P-gp, respectively, however, the involvement of other transporters and the clinical relevance of such interaction still need to be clarified. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|