Progress in the Consideration of Possible Sex Differences in Drug Interaction Studies

2019 ◽  
Vol 20 (2) ◽  
pp. 114-123 ◽  
Author(s):  
Panjasaram Naidoo ◽  
Manoranjenni Chetty
Keyword(s):  
Sex Differences ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Qt Prolongation ◽  
Equal Proportion ◽  
Anecdotal Evidence ◽  
Interaction Studies ◽  
Males And Females ◽  
General Guidance

Background: Anecdotal evidence suggests that there may be sex differences in Drug-drug Interactions (DDI) involving specific drugs. Regulators have provided general guidance for the inclusion of females in clinical studies. Some clinical studies have reported sex differences in the Pharmacokinetics (PK) of CYP3A4 substrates, suggesting that DDI involving CYP3A4 substrates could potentially show sex differences. Objective: The aim of this review was to investigate whether recent prospective DDI studies have included both sexes and whether there was evidence for the presence or absence of sex differences with the DDIs. Methods: The relevant details from 156 drug interaction studies within 124 papers were extracted and evaluated. Results: Only eight studies (five papers) compared the outcome of the DDI between males and females. The majority of the studies had only male volunteers. Five studies had females only while 60 had males only, with 7.7% of the studies having an equal proportion of both sexes. Surprisingly, four studies did not specify the sex of the subjects. : Based on the limited number of studies comparing males and females, no specific trends or conclusions were evident. Sex differences in the interaction were reported between ketoconazole and midazolam as well as clarithromycin and midazolam. However, no sex difference was observed with the interaction between clarithromycin and triazolam or erythromycin and triazolam. No sex-related PK differences were observed with the interaction between ketoconazole and domperidone, although sex-related differences in QT prolongation were observed. Conclusion: This review has shown that only limited progress had been made with the inclusion of both sexes in DDI studies.

scholarly journals Herb–Drug Interactions: Worlds Intersect with the Patient at the Center

Medicines ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 44
Author(s):  
Mary Beth Babos ◽  
Michelle Heinan ◽  
Linda Redmond ◽  
Fareeha Moiz ◽  
Joao Victor Souza-Peres ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Case Report ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Drug Information ◽  
Case Reports ◽  
Full Information ◽  
Information Need ◽  
Herbal Products ◽  
Reduce Risk

This review examines three bodies of literature related to herb–drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case reports signal for further study. A qualitative review of case reports seeks to determine needs and perspectives of case report authors. Methods: Systematic search of Medline identified clinical studies and case reports of interacting herb–drug combinations. Interacting herb–drug pairs were searched in six drug interaction resources. Case reports were analyzed qualitatively for completeness and to identify underlying themes. Results: Ninety-nine case-report documents detailed 107 cases. Sixty-five clinical studies evaluated 93 mechanisms of interaction relevant to herbs reported in case studies, involving 30 different herbal products; 52.7% of these investigations offered evidence supporting reported reactions. Cohen’s kappa found no agreement between any interaction checker and case report corpus. Case reports often lacked full information. Need for further information, attitudes about herbs and herb use, and strategies to reduce risk from interaction were three primary themes in the case report corpus. Conclusions: Reliable herb–drug information is needed, including open and respectful discussion with patients.

scholarly journals Sex Differences in Substance Use Disorders: A Neurobiological Perspective

2021 ◽  
Vol 2 ◽  
Author(s):  
Jennifer L. Cornish ◽  
Asheeta A. Prasad
Keyword(s):  
Substance Use ◽  
Sex Differences ◽  
Clinical Studies ◽  
Reward Processing ◽  
Future Research ◽  
Neural Structure ◽  
Patterns Of Use ◽  
Males And Females ◽  
Potential Impact ◽  
Advance Knowledge

Clinical studies provide fundamental knowledge of substance use behaviors (substance of abuse, patterns of use, relapse rates). The combination of neuroimaging approaches reveal correlation between substance use disorder (SUD) and changes in neural structure, function, and neurotransmission. Here, we review these advances, placing special emphasis on sex specific findings from structural neuroimaging studies of those dependent on alcohol, nicotine, cannabis, psychostimulants, or opioids. Recent clinical studies in SUD analyzing sex differences reveal neurobiological changes that are differentially impacted in common reward processing regions such as the striatum, hippocampus, amygdala, insula, and corpus collosum. We reflect on the contribution of sex hormones, period of drug use and abstinence, and the potential impact of these factors on the interpretation of the reported findings. With the overall recognition that SUD impacts the brains of females and males differentially, it is of fundamental importance that future research is designed with sex as a variable of study in this field. Improved understanding of neurobiological changes in males and females in SUD will advance knowledge underlying sex-specific susceptibility and the neurobiological impact in these disorders. Together these findings will inform future treatments that are tailor designed for improved efficacy in females and males with SUD.

Potential Drug Interactions— Fact or Fallacy?

1975 ◽  
Vol 9 (11) ◽  
pp. 586-590 ◽  
Author(s):  
Curtis D. Black ◽  
Nicholas G. Popovich
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Patient Care ◽  
Clinical Studies ◽  
Literature Search ◽  
Potential Drug ◽  
Careful Evaluation ◽  
Current Drug ◽  
Drug Drug Interaction

At present, the pharmacist is faced with a perplexing number of potential drug interactions as they relate to patient care. The purpose of the investigation was to evaluate current drug-drug interaction literature, specifically gastrointestinal drug interactions. Literature search and review evaluated the authoritative basis on which conclusions were made. From this, a review was written to illustrate fallacies and misconceptions that could be derived from the literature with the intent it would serve as a guide in interpreting and evaluating drug-drug interactions. The overall study illustrates the vast need for careful evaluation of drug interaction literature before erroneous recommendations are made on conceivably inconclusive clinical studies.

2020 FDA Drug-drug Interaction Guidance: A Comparison Analysis and Action Plan by Pharmaceutical Industrial Scientists

2020 ◽  
Vol 21 (6) ◽  
pp. 403-426 ◽  
Author(s):  
Sirimas Sudsakorn ◽  
Praveen Bahadduri ◽  
Jennifer Fretland ◽  
Chuang Lu
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Action Plan ◽  
European Medicines Agency ◽  
Cytochrome P450 Enzyme ◽  
Interaction Studies ◽  
P450 Enzyme ◽  
Us Fda

Background: In January 2020, the US FDA published two final guidelines, one entitled “In vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry” and the other entitled “Clinical Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry”. These were updated from the 2017 draft in vitro and clinical DDI guidance. Methods: This study is aimed to provide an analysis of the updates along with a comparison of the DDI guidelines published by the European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) along with the current literature. Results: The updates were provided in the final FDA DDI guidelines and explained the rationale of those changes based on the understanding from research and literature. Furthermore, a comparison among the FDA, EMA, and PMDA DDI guidelines are presented in Tables 1, 2 and 3. Conclusion: The new 2020 clinical DDI guidance from the FDA now has even higher harmonization with the guidance (or guidelines) from the EMA and PMDA. A comparison of DDI guidance from the FDA 2017, 2020, EMA, and PMDA on CYP and transporter based DDI, mathematical models, PBPK, and clinical evaluation of DDI is presented in this review.

Assessment of Herb-Drug Interactions Based on the Pharmacokinetic Changes of Probe Drug, Midazolam

2020 ◽  
Vol 14 ◽  
Author(s):  
Sarvesh Sabarathinam ◽  
Thangavel Mahalingam Vijayakumar
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Healthy Volunteers ◽  
Clinical Studies ◽  
Half Life ◽  
Clinical Evidence ◽  
High Dose ◽  
Online Database ◽  
Probe Drug

Background: In healthy volunteers, the probe drug method is widely practised to assess the pharmacokinetic mediated herb-drug interactions (HDI). We analyzed the clinical evidence of CYP3A4 probe drug, Midazolam. Methods: Literatures where Midazolam was used as a probe drug for prediction of herb-drug interaction was survey through an online database such as google scholar, Scopus, Cochrane, PubMed and clinicaltrials.gov. Results: Midazolam was considered as a sensitive probe for CYP3A4 substrates due to its bioavailability. We observed that not all the herbs are causing drug interaction. However, significant changes of the Midazolam pharmacokinetics were found after high-dose and long-term intake of some herbs and food supplements, Suggesting the induction and/or inhibition of CYP activities. Conclusion: Probe drug technique is one of the easiest ways for predicting CYP enzyme-mediated herb-drug interactions. Midazolam shows a good response in clinical studies because of short half-life and low harmfulness compared with other probe drugs.

scholarly journals Drug-Drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review

2020 ◽  
Author(s):  
Beatriz Oda Plasencia-Garcia ◽  
Gonzalo Rodriguez-Menendez ◽  
Maria Isabel Rico-Rangel ◽  
Ana Rubio-Garcia ◽  
Jaime Torello-Iserte ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Qt Prolongation ◽  
Evidence Based ◽  
Behavioral Disturbances ◽  
Pharmacological Management ◽  
Evidence Review ◽  
Evidence Based Guidelines ◽  
Selection Of

Relevance: Management of symptoms like anxiety, delirium and agitation cannot be neglected in COVID-19 patients. Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored Objective: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Evidence Review: Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c) Liverpool Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and TdP, the CredibleMeds QTDrugs List was searched. Based on the information collected, the authors made a recommendation agreed to by consensus. In addition, a systematic review was conducted to find the clinical outcomes of drug-drug interactions between COVID-19 treatments and antipsychotics Results: The main interaction between COVID-19 drugs and antipsychotics are the risk of QT prolongation and TdP, and CYP interactions. Remdesivir, favipiravir, baricinitib, and anakinra can be used concomitantly with antipsychotics with no risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Tocilizumab is rather safe to use in combination with antipsychotics, although it can restore the activity of CYP3A4 and therefore its substrate metabolism may increase. The most demanding COVID-19 treatments for co-administration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin (all prolong QT interval) and lopinavir / ritonavir (CYP interaction and risk of QT prolongation). Conclusions: We urge to development of evidence-based guidelines that can help clinicians decide the safest treatment combination and monitoring necessary for each particular patient. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored.

Review on Preclinical and Clinical Evidence of Food (Beverages, Fruits and Vegetables) and Drug Interactions: Mechanism and Safety

2020 ◽  
Vol 15 (1) ◽  
pp. 12-27 ◽  
Author(s):  
Yogesh C. Yadav ◽  
Kamla Pathak ◽  
Devender Pathak
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Fruits And Vegetables ◽  
Therapeutic Response ◽  
Therapeutic Potential ◽  
Specific Interaction ◽  
Interaction Mechanism ◽  
Food Composition ◽  
Dietary Habit

Background:The therapeutic potency and efficacy of drugs can be affected by a patient’s dietary habit. The food composition and their nutritional value interact with drugs that lead to alteration of the therapeutic response of drugs in patients.Objective:This present review is an attempt to illustrate clinical reports of food-drug interaction. Further, it also highlights specific interaction mechanism(s) and the safety thereof.Methods:Through the search engine “Scopus”; literature on recent advances in food and drug interactions includes almost all therapeutic categories such as antimicrobials, antiviral, antifungal, antihistamines, anticoagulants, non-steroidal anti-inflammatory drugs, and drugs acting on the central nervous system and cardiovascular system.Results:Preclinical and clinical studies that have been conducted by various researchers affirm significant drug-food interactions across the various therapeutic categories of drugs. Preclinical studies have documented the effects of food, milk products, alcohols, fruit and vegetables on the drug absorption, metabolizing enzymes and drug transporters. The clinical studies on fruits/vegetables and drugs interactions report significant alteration in therapeutic response.Conclusion:Based on the preclinical and clinical reports, it can be concluded that the interaction of food with drug(s) significantly alters their therapeutic potential. The inputs from clinical practitioners to elucidate potential risk of food-drug interaction need to be intensified in order to prevent adverse clinical consequences.

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