The in vitro metabolism of FK 506 and its inhibition by other drugs was studied with hepatic microsomes from rats pre-treated with dexamethasone, a selective cytochrome P-450 IIIA inducer. Nonspecific inhibitors of cytochrome P-450, such as ketoconazole, itraconazole, fluconazole and SKF 525 A, and most of the cytochrome P-450 IIIA specific substrates used in this study significantly inhibited FK 506 metabolism. Although cyclosporine is a known substrate of cytochrome P-450 IIIA, it had no effect on FK 506 metabolism. Cytochrome P-450 II substrates had minimal but significant effect on FK 506 metabolism. This data supports our earlier observations that FK 506 metabolism is mediated predominantly by the steroid inducible cytochrome P-450 IIIA enzyme subfamily. The results of this study indicate that in transplant patients there is a potential for an interaction of FK 506 with other drugs that are metabolized by the cytochrome P-450 IIIA subfamily or those that alter the activity of cytochrome P-450 IIIA subfamily. Careful monitoring and FK 506 dosing adjustment may be necessary to maintain therapeutic concentration and minimize toxicity in patients receiving this agent.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations.
Sci Rep
January 2025
Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706, Santiago de Compostela, Spain.
Aripiprazole (ARI) is an atypical antipsychotic which is a substrate of P-glycoprotein (P-gp), a transmembrane glycoprotein that plays a crucial role in eliminating potentially harmful compounds from the organism. ARI once-monthly (AOM) is a long-acting injectable form which improves treatment compliance. Genetic polymorphisms in ABCB1 may lead to changes in P-gp function, leading to individual differences in drug disposition.
View Article and Find Full Text PDFBackground: Polyunsaturated fatty acids are metabolized by cytochrome P450 (CYP450) into anti-inflammatory, pro-resolving epoxides, which are rapidly converted to inactive and cytotoxic diols by soluble epoxide hydrolase (sEH). Increased CYP450-sEH metabolites are associated with worse cognition in type 2 diabetes mellitus (T2DM), and greater white matter hyperintensities (WMH) in patients with stroke. We examined whether the relationship between linoleic acid (LA)-derived CYP450-sEH metabolites (oxylipins) and small vessel disease (SVD) markers differ across diabetes status.
View Article and Find Full Text PDFDeveloping Topics.
Alzheimers Dement
December 2024
Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Background: Aging and the decline in sex steroid hormone (e.g., estrogen) are associated with a potential loss of its neuroprotective effects on the female brain.
View Article and Find Full Text PDFBackground: Alzheimer's Disease ("AD") presents a significant global health burden, often requiring medication management of comorbidities, some of which are metabolized by the polymorphic enzyme CYP2C9. We investigated the impact of CYP2C9 polymorphism on the reduction of Neuropsychiatric Inventory (NPI-12) scores following administration of IGC-AD1, comprising THC and melatonin, in AD patients.
Method: Thirteen Puerto Rican AD patients (mean age: 80.
Background: Alzheimer's disease (AD) affects millions of Americans, with potential future increases without breakthroughs in treatment. IGC-AD1, a novel formulation comprising of delta-9 tetrahydrocannabinol ("THC") and melatonin, is being studied in AD-associated agitation. THC is predominantly metabolized by cytochrome P450 and specifically by CYP2C9.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!