scholarly journals Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1180
Author(s):  
Danuta Szkutnik-Fiedler
Keyword(s):  
Monoclonal Antibodies ◽  
Drug Interactions ◽  
New Drugs ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Calcitonin Gene ◽  
The Us ◽  
Cyp3a4 Inhibitors ◽  
Serotonergic Drugs

In the last few years, there have been significant advances in migraine management and prevention. Lasmiditan, ubrogepant, rimegepant and monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) are new drugs that were launched on the US pharmaceutical market; some of them also in Europe. This publication reviews the available worldwide references on the safety of these anti-migraine drugs with a focus on the possible drug–drug (DDI) or drug–food interactions. As is known, bioavailability of a drug and, hence, its pharmacological efficacy depend on its pharmacokinetics and pharmacodynamics, which may be altered by drug interactions. This paper discusses the interactions of gepants and lasmiditan with, i.a., serotonergic drugs, CYP3A4 inhibitors, and inducers or breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) inhibitors. In the case of monoclonal antibodies, the issue of pharmacodynamic interactions related to the modulation of the immune system functions was addressed. It also focuses on the effect of monoclonal antibodies on expression of class Fc gamma receptors (FcγR).

scholarly journals Drug – Drug Interactions Between Newer Anti- Retroviral Drugs And Anti Epileptics - A Review

2020 ◽  
Vol 11 (3) ◽  
pp. 2963-2967
Author(s):  
Vaishnavi S ◽  
Balaji S ◽  
Ramesh M ◽  
Mothi S N ◽  
Swamy V H T ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Drug Interactions ◽  
Drug Toxicity ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Immunodeficiency Virus ◽  
Pharmacokinetic Properties ◽  
Mechanism Of Interaction ◽  
Cyp 3A

Drug – Drug Interactions (DDIs) are the leading cause of drug toxicity and emergence of drug resistance, ultimately leading to increased burden in People Living with Human Immunodeficiency Virus (PLHIV). On an average 55 % of people on Anti Retroviral Therapy (ARVs) are co-administered with Anti Epileptic Drugs (AEDs). The introduction of newer anti-retroviral drugs such as dolutegravir, bictegravir, emtricitabine, doravirine are proven to have less side effects, high tolerability and effective decrease in the viral load, but the risk of DDIs still stands to be high. This review briefly describes about the pharmacokinetic properties of dolutegravir, bictegravir, emtricitabine, doravirine, mechanism of interaction between the above mentioned ARVs and AEDs, effect of DDIs on ARVs, effect of DDIs on interacting AEDs, outcome of DDIs and possible management of DDIs. The pharmacokinetic type of DDIs was observed between the ARVs and AEDs. The majority of DDIs were found affecting the metabolism and the absorption of the drugs. UGT1A1, CYP 3A are the two important classes of metabolic enzymes involved in the DDIs and p- glycoprotein (P-gp) is the transporter involved in the DDIs affecting the absorption. Significant interactions have been found in between the above mentioned newer ARV’s with carbamazepine, oxcarbazepine, phenytoin and phenobarbitol.

Posaconazole–digoxin drug–drug interaction mediated by inhibition of P-glycoprotein

2018 ◽  
Vol 25 (7) ◽  
pp. 1758-1761 ◽  
Author(s):  
Abby C Shumaker ◽  
Heather M Bullard ◽  
Jane Churpek ◽  
Randall W Knoebel
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Antifungal Agents ◽  
Polymorphic Ventricular Tachycardia ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Ventricular Response ◽  
Clinically Significant ◽  
P450 Isozymes ◽  
Cytochrome P450 Isozymes

Drug–drug interactions between digoxin and the triazole antifungal agents, mediated via various cytochrome P450 isozymes, have been described in the literature. Posaconazole is not extensively metabolized by these isozymes but is both a p-glycoprotein (P-gp) substrate and inhibitor. To our knowledge, there have been no published cases of clinically significant posaconazole-digoxin drug–drug interactions. We report an interaction between posaconazole (300 mg by mouth daily) and digoxin (0.25 mg by mouth daily, Monday through Friday) resulting in atrial fibrillation with slow ventricular response and degenerating into polymorphic ventricular tachycardia.

The next generation of machine learning in DDIs prediction

2021 ◽  
Vol 27 ◽  
Author(s):  
Wei Huang ◽  
Chunyan Li ◽  
Ying Ju ◽  
Yan Gao
Keyword(s):  
Drug Interactions ◽  
Adverse Reactions ◽  
Computational Method ◽  
New Drugs ◽  
Computational Techniques ◽  
Data Sets ◽  
Review Of The Literature ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Challenges And Opportunities ◽  
Drug Assays

: Drug-drug interactions may occur when to combine two or more drugs and may cause some adverse events such as Cardiotoxicity, Central neurotoxicity, Hepatotoxicity, etc. Although a large number of researchers who are proficient in pharmacokinetics and pharmacodynamics have been engaged in drug assays and trying to find out the side effects of all kinds of drug combinations. However, at the same time, the number of new drugs is increasing dramatically, and the drug assay is an expensive and time-consuming process. It is impossible to find all the adverse reactions through drug experiments. Therefore, new attempts have risen in using computational techniques to deal with this problem. In this review, we conduct a review of the literature on applying the computational method for predicting drug-drug interactions. We first briefly introduce the widely used data sets. After that, we elaborate on the existing state-of-art deep learning models for drug-drug interactions prediction. We also discussed the challenges and opportunities of applying the computational method in drug-drug interactions prediction.

Interactions between cardiology and oncology drugs in precision cardio-oncology

2021 ◽  
Vol 135 (11) ◽  
pp. 1333-1351
Author(s):  
Sailaja Kamaraju ◽  
Meera Mohan ◽  
Svetlana Zaharova ◽  
Brianna Wallace ◽  
Joseph McGraw ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Treatment Approach ◽  
Interdisciplinary Collaboration ◽  
Multidisciplinary Treatment ◽  
Close Attention ◽  
Glycoprotein P ◽  
Patients With Cancer ◽  
P Glycoprotein ◽  
Cardiovascular Side Effects

Abstract Recent advances in treatment have transformed the management of cancer. Despite these advances, cardiovascular disease remains a leading cause of death in cancer survivors. Cardio-oncology has recently evolved as a subspecialty to prevent, diagnose, and manage cardiovascular side effects of antineoplastic therapy. An emphasis on optimal management of comorbidities and close attention to drug interactions are important in cardio-oncologic care. With interdisciplinary collaboration among oncologists, cardiologists, and pharmacists, there is potential to prevent and reduce drug-related toxicities of treatments. The cytochrome P450 (CYP450) family of enzymes and the P-glycoprotein (P-g) transporter play a crucial role in drug metabolism and drug resistance. Here we discuss the role of CYP450 and P-g in drug interactions in the field of cardio-oncology, provide an overview of the cardiotoxicity of a spectrum of cancer agents, highlight the role of precision medicine, and encourage a multidisciplinary treatment approach for patients with cancer.

scholarly journals INFLUENCE OF LOVASTATIN ON PHARMACOKINETICS AND PHARMACODYNAMICS OF GLIPIZIDE IN HEALTHY AND STREPTOZOTOCIN - INDUCED DIABETIC RATS: INVOLVEMENT OF P-GLYCOPROTEIN INHIBITION

2016 ◽  
Vol 9 (5) ◽  
pp. 3
Author(s):  
Kishore Kumar Kadimpati ◽  
Vanishree Sammeta ◽  
Ravindra Babu Pingili ◽  
Dr. Sujatha Sanneboina
Keyword(s):  
Multiple Dose ◽  
Diabetic Rats ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Glycoprotein P ◽  
Multiple Dose Study ◽  
P Glycoprotein ◽  
Dose Study ◽  
Glycoprotein Inhibition ◽  
Everted Sacs

ABSTRACTThis study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduceddiabeticrats.In singledose study(SDS), blood samples werecollectedonthe 1st day, whereas in multiple dose study on the 15 day at0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The C of Gpz wasincreased from 2.97 to 8.38 and 9.87 to 24.58 ng/mL in healthy and diabetic rats, respectively, in multiple dose study. Rat everted sacs were used tostudy the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosalsurface was significantly increased from 4.32 to 5.65 and 6.02 µg/mL in the presence of Lov and verapamil, respectively. The interaction between Lovand Gpz is due to P-gp and CYP2C9 inhibition.Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.maxth

scholarly journals Docking Applied to the Prediction of the Affinity of Compounds to P-Glycoprotein

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Pablo H. Palestro ◽  
Luciana Gavernet ◽  
Guillermina L. Estiu ◽  
Luis E. Bruno Blanch
Keyword(s):  
Experimental Data ◽  
Virtual Screening ◽  
Rational Design ◽  
Careful Analysis ◽  
New Drugs ◽  
Drug Resistant ◽  
Autodock Vina ◽  
Flexible Docking ◽  
Glycoprotein P ◽  
P Glycoprotein

P-glycoprotein (P-gp) is involved in the transport of xenobiotic compounds and responsible for the decrease of the drug accumulation in multi-drug-resistant cells. In this investigation we compare several docking algorithms in order to find the conditions that are able to discriminate between P-gp binders and nonbinders. We built a comprehensive dataset of binders and nonbinders based on a careful analysis of the experimental data available in the literature, trying to overcome the discrepancy noticeable in the experimental results. We found that Autodock Vina flexible docking is the best choice for the tested options. The results will be useful to filter virtual screening results in the rational design of new drugs that are not expected to be expelled by P-gp.

scholarly journals Interaction of Common Azole Antifungals with P Glycoprotein

2002 ◽  
Vol 46 (1) ◽  
pp. 160-165 ◽  
Author(s):  
Er-jia Wang ◽  
Karen Lew ◽  
Christopher N. Casciano ◽  
Robert P. Clement ◽  
William W. Johnson
Keyword(s):  
Drug Interactions ◽  
Transport Activity ◽  
Glycoprotein P ◽  
Azole Antifungals ◽  
Atp Binding Cassette Transporter ◽  
P Glycoprotein ◽  
A Cell ◽  
Clinical Interactions ◽  
Clinical Drug

ABSTRACT Both eucaryotic and procaryotic cells are resistant to a large number of antibiotics because of the activities of export transporters. The most studied transporter in the mammalian ATP-binding cassette transporter superfamily, P glycoprotein (P-gp), ejects many structurally unrelated amphiphilic and lipophilic xenobiotics. Observed clinical interactions and some in vitro studies suggest that azole antifungals may interact with P-gp. Such an interaction could both affect the disposition and exposure to azole antifungal therapeutics and partially explain the clinical drug interactions observed with some antifungals. Using a whole-cell assay in which the retention of a marker substrate is evaluated and quantified, we studied the abilities of the most widely prescribed orally administered azole antifungals to inhibit the function of this transporter. In a cell line presenting an overexpressed amount of the human P-gp transporter, itraconazole and ketoconazole inhibited P-gp function with 50% inhibitory concentrations (IC50s) of ∼2 and ∼6 μM, respectively. Cyclosporin A was inhibitory with an IC50 of 1.4 μM in this system. Uniquely, fluconazole had no effect in this assay, a result consistent with known clinical interactions. The effects of these azole antifungals on ATP consumption by P-gp (representing transport activity) were also assessed, and the K m values were congruent with the IC50s. Therefore, exposure of tissue to the azole antifungals may be modulated by human P-gp, and the clinical interactions of azole antifungals with other drugs may be due, in part, to inhibition of P-gp transport.

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