Herb-drug Interactions Research Articles

Herb-drug interactions: A short review on central and peripheral nervous system drugs.

Herbal medicines are widely perceived as natural and safe remedies. However, their concomitant use with prescribed drugs is a common practice, often undertaken without full awareness of the potential risks and frequently without medical supervision. This practice introduces a tangible risk of herb-drug interactions, which can manifest as a spectrum of consequences, ranging from acute, self-limited reactions to unpredictable and potentially lethal scenarios. This review offers a comprehensive overview of herb-drug interactions, with a specific focus on medications targeting the Central and Peripheral Nervous Systems. Our work draws upon a broad range of evidence, encompassing preclinical data, animal studies, and clinical case reports. We delve into the intricate pharmacodynamics and pharmacokinetics underpinning each interaction, elucidating the mechanisms through which these interactions occur. One pressing issue that emerges from this analysis is the need for updated guidelines and sustained pharmacovigilance efforts. The topic of herb-drug interactions often escapes the attention of both consumers and healthcare professionals. To ensure patient safety and informed decision-making, it is imperative that we address this knowledge gap and establish a framework for continued monitoring and education. In conclusion, the use of herbal remedies alongside conventional medications is a practice replete with potential hazards. This review not only underscores the real and significant risks associated with herb-drug interactions but also underscores the necessity for greater awareness, research, and vigilant oversight in this often-overlooked domain of healthcare.

Herb-drug interactions of silybinin and cilofexor in beagle dogs based on pharmacokinetics by UPLC-MS/MS.

Objective: A remarkably sensitive, accurate, and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed as a facile and expeditious method for measuring cilofexor concentration in beagle dogs, the herb-drug interactions between silybinin and cilofexor was explored based on pharmacokinetics. Methods: The plasma sample protein of the beagles were rapidly sedimented with acetonitrile, and cilofexor and tropifexor (internal standard, ISTD) were separated by gradient elution using a 0.1% formic acid aqueous solution and acetonitrile as the mobile phase. The concentrations were detected using positive ion multiple reaction monitoring (MRM) mode. Mass transfer pairs were m/z 587.91→267.91 for cilofexor and m/z 604.08→228.03 for ISTD, respectively. A two-period self-controlled experimental design was adopted for the HDIs experiment. In the first period (Group A), six beagle dogs were orally administered cilofexor at a dose of 1mg/kg. In the second period (Group B), silybinin (3mg/kg) was orally administered to the six beagle dogs twice a day for seven consecutive days, after which cilofexor was orally administered. The cilofexor concentration in beagle dogs was determined, and HDIs were evaluated based on their pharmacokinetics. Results: The accuracy and precision of cilofexor were both less than 15%, and the recoveries, matrix effects, and stability met the relevant requirements. The Cmax of cilofexor in group B was 49.62% higher than that in group A, whereas the AUC(0-t) and AUC(0-∞) of cilofexor in group B were 47.85% and 48.52% higher, respectively, than those in group A. Meanwhile, the t1/2 extended from 7.84h to 9.45 h, CL and Vz decreased in Group B. Conclusion: A novel UPLC-MS/MS approach was successfully applied for the measurement of cilofexor in beagle dog plasma. Silybinin can alter the pharmacokinetics of cilofexor in beagle dogs, thereby increasing plasma exposure to cilofexor.

Exploring pharmacokinetics and herb-drug interactions of an herbal extract mixture derived from Poria cocos and Morus alba L.

Exploring pharmacokinetics and herb-drug interactions of an herbal extract mixture derived from Poria cocos and Morus alba L.

Evidence of the interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and Chinese herbal medicine: A scoping review

ObjectivesChinese herbal medicine (CHM) has been shown to be effective in autoimmune rheumatic diseases, but harmful herb-drug interactions might be inherent. We aim to review the evidence regarding herb-drug interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and CHM. MethodsWe searched PubMed, EMBASE and CINAHL from inception till 30 April 2023 using keywords that encompassed ‘herb-drug interactions’, ‘herbs’ and ‘immunosuppressants’. Articles were included if they contained reports about interactions between immunosuppressive drugs used in the treatment of rheumatic diseases with CHM. Level of evidence for each pair of interaction was graded using the algorithm developed by Colalto. ResultsA total of 65 articles and 44 unique pairs of interactions were identified. HDIs were reported for cyclophosphamide, cyclosporine, tacrolimus, methotrexate, mycophenolic acid, glucocorticoids, sulfasalazine, tofacitinib and biologic disease-modifying antirheumatic drugs. Among these, cyclosporine (n = 27, 41.5%) and tacrolimus (n = 19, 29.2%) had the highest number of documented interactions. Hypericum perforatum had the highest level of evidence of interaction with cyclosporine and tacrolimus. Consumption reduced the bioavailability and therapeutic effects of the drugs. Schisandra sphenanthera had the highest level of evidence of interaction with tacrolimus and increased the bioavailability of the drug. Majority of the articles were animal studies. ConclusionOverall level of evidence for the included studies were low, though interactions between cyclosporine, tacrolimus, Hypericum perforatum and Schisandra sphenanthera were the most and well-documented. Healthcare professionals should actively enquire about the concurrent use of CHM in patients, especially when drugs with a narrow therapeutic index are consumed.

Safety Aspects of Herb Interactions: Current Understanding and Future Prospects.

The use of herbal medicines is on the rise throughout the world due to their perceived safety profile. However, incidences of herb-drug, herb-herb and herb-food interactions considering safety aspects have opened new arenas for discussion. The current study aims to provide comprehensive insights into the various types of herb interactions, the mechanisms involved, their assessment, and historical developments, keeping herbal safety at the central point of discussion. The authors undertook a focused/targeted literature review and collected data from various databases, including Science Direct, Wiley Online Library, Springer, PubMed, and Google Scholar. Conventional literature on herbal remedies, such as those by the WHO and other international or national organizations. The article considered reviewing the regulations, interaction mechanisms, and detection of herb-herb, herb-drug and herb-food interactions in commonly used yet vital plants, including Glycyrrhiza glabra, Mentha piperita, Aloe barbadensis, Zingiber officinale, Gingko biloba, Withania somnifera, etc. The study found that healthcare professionals worry about patients not informing them about their herbal prescriptions (primarily used with conventional treatment), which can cause herb-drug/herb-food/herb-herb interactions. These interactions were caused by altered pharmacodynamic and pharmacokinetic processes, which might be explained using in-vivo, in-vitro, in-silico, pharmacogenomics, and pharmacogenetics. Nutrivigilance may be the greatest method to monitor herb-food interactions, but its adoption is limited worldwide. This article can serve as a lead for clinicians, guiding them regarding herb-drug, herb-food, and herb-herb interactions induced by commonly consumed plant species. Patients may also be counseled to avoid conventional drugs, botanicals, and foods with a restricted therapeutic window.

Developing implementation strategies for promoting integrative oncology outpatient service delivery and utilisation: a qualitative study in Hong Kong.

Current evidence supports the use of integrative oncology (IO) interventions in cancer supportive care. The demand for outpatient IO services in Hong Kong is expected to soar following the surge in cancer incidence due to population ageing. This study identified the factors influencing the delivery and utilisation of outpatient IO from local stakeholders' perspectives and developed corresponding implementation strategies. This study involved two sequential stages. First, with individual semi-structured interviews guided by the Theoretical Domains Framework (TDF), we explored stakeholders' views on the barriers to and facilitators for implementing IO. Second, guided by a TDF-based qualitative data analysis of interview transcripts, we performed intervention mapping to develop Behaviour Change Wheel-based implementation strategies that may overcome the barriers and strengthen the facilitators. We interviewed 31 stakeholders, including traditional Chinese medicine (TCM) practitioners (n = 8), biomedically-trained doctors (n = 7), nurses (n = 6), administrators (n = 4), caregivers (n = 4), and pharmacists (n = 2). The key local factors influencing outpatient IO are (1) lacking nursing and administrative workforce supporting IO service delivery, (2) lacking awareness of IO services among healthcare professionals, administrators, patients, and caregivers, and (3) lacking knowledge among healthcare professionals of herb-drug interaction and herbal toxicities. We recommended a multi-faceted implementation strategies package that included arranging funding to train, recruit, and retain nursing and administrative staff, devolving resources into promoting interprofessional collaborations and evidence on IO effectiveness and safety, integrating evidence on herb-drug interactions and herbal toxicities into automated electronic health record systems monitored by pharmacists with dual qualifications in TCM and conventional pharmacy.

Immunization against Medically Important Human Coronaviruses of Public Health Concern.

SARS-CoV-2 is a virus that affects the human immune system. It was observed to be on the rise since the beginning of 2020 and turned into a life-threatening pandemic. Scientists have tried to develop a possible preventive and therapeutic drug against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and other related coronaviruses by assessing COVID-19-recovered persons' immunity. This study aims to review immunization against SARS-CoV-2, along with exploring the interventions that have been developed for the prevention of SARS-CoV-2. This study also highlighted the role of phototherapy in treating SARS-CoV infection. The study adopted a review approach to gathering the information available and the progress that has been made in the treatment and prevention of COVID-19. Various vaccinations, including nucleotide, subunit, and vector-based vaccines, as well as attenuated and inactivated forms that have already been shown to have prophylactic efficacy against the Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, have been summarized. Neutralizing and non-neutralizing antibodies are all associated with viral infections. Because there is no specific antiviral vaccine or therapies for coronaviruses, the main treatment strategy is supportive care, which is reinforced by combining broad-spectrum antivirals, convalescent plasma, and corticosteroids. COVID-19 has been a challenge to keep reconsidering the usual approaches to regulatory evaluation as a result of getting mixed and complicated findings on the vaccines, as well as licensing procedures. However, it is observed that medicinal herbs also play an important role in treating infection of the upper respiratory tract, the principal symptom of SARS-CoV due to their natural bioactive composite. However, some Traditional Chinese Medicines contain mutagens and nephrotoxins and the toxicological properties of the majority of Chinese herbal remedies are unknown. Therefore, to treat the COVID-19 infection along with conventional treatment, it is recommended that herb-drug interaction be examined thoroughly.

In vivo assessment of black seed oil single dose on prednisolone pharmacokinetics.

To investigate the effect of blackseed oil (BSO) single dose on prednisolone pharmacokinetics via p-gp inhibition. Three groups of rats (n = 5) were orally administered the vehicle, verapamil (50 mg/kg) or BSO (5 ml/kg) 15 min prior to prednisolone (5 mg/kg) administration. Blood samples were collected over 24 h and quantified. Non-compartmental analysis was employed to calculate maximum plasma concentration (Cmax), area under the curve (AUC0-last), time to reach Cmax (Tmax), apparent clearance (CL/F), and half-life (t1/2). Statistical significance was considered at p<0.05. Prednisolone Cmax and AUC0-last decreased by 65% and 25% in the BSO group compared to the negative control (P < .0001, .0029, respectively) while they increased by 1.75-folds and 8-folds in verapamil group (P < .0001). Tmax was achieved at 0.16, 0.5, and 0.25 h in the negative control, verapamil, and BSO-treated groups, respectively. CL/F in the treatment group was 1.3-fold and 10-fold higher compared to the negative and positive control, respectively, whereas the t1/2 remained comparable. Administration of BSO decreased prednisolone Cmax and AUC0-last in rats indicating that there is a herb-drug interaction; however, p-gp inhibition cannot be concluded. Patients relying on folk medicine in chronic illnesses treatment might need to avoid combining BSO with prednisolone.

Artificial intelligence in Ayurveda: Current concepts and prospects

Abstract Background: Artificial intelligence (AI) has become a powerful tool in health care, and its integration with Ayurveda, presents promising opportunities. Aims: This review aims to Explore AI’s role in enhancing Ayurvedic diagnosis, personalized treatments, and drug discovery, challenges related to AI integration in Ayurveda. Methods and Materials: A comprehensive literature search was conducted to identify relevant studies and articles on the integration of AI and Ayurveda. The search included databases such as PubMed, Google Scholar, and relevant journals. The collected data were analyzed to present a comprehensive overview of the topic. Results: AI algorithms analyze patient data to enhance accuracy in diagnosis. They can integrate genomic, lifestyle, and environmental data for precise Prakriti determination. AI can digitize traditional diagnostic tools for standardization, such as pulse and tongue examination. AI tailors personalized treatments based on an individual’s constitution and imbalances. AI accelerates the discovery of medicinal herbs and predicts herb-drug interactions. It formulates personalized herbal combinations, preserving traditional knowledge. AI-driven health monitoring provides personalized lifestyle recommendations based on Ayurvedic principles. Conclusions: The integration of AI into Ayurveda holds promise in transforming traditional medicine and health care. Collaboration between Ayurvedic practitioners, technology experts, and policymakers is essential to address challenges. The future prospects of AI in Ayurveda are bright, offering personalized treatments, preventive health care, and research advancements while preserving Ayurveda’s holistic essence.

Mitigating the Risks of Herb-Drug Interaction among Artisans in Ibadan Metropolis Through Public Health Education Survey

Background: Globally, there has been an increase in the use of herbal medicines with the general misconception that herbal medicines are absolutely effective and safe. Many people often use herbs concomitantly with orthodox medicines and this may lead to fatal complications of herb-drug interactions. This cross-sectional survey assesses the knowledge and attitude of teachers and artisans on the use of herbal medicine and the possible occurrence of herb-herb and herb-drug interactions.&#x0D; Method: A semi-structured questionnaire was used which covered demographics, cultural categorization of herbal medicine used, socio-economic factors (SEF), reason(s) for herbal medicine use, knowledge of herb-herb (HHI) and herb-drug interactions (HDI) and, and attitude to herbal medications (AHM) of the respondents. Data were entered into SPSS version 20 and analyzed using descriptive and inferential statistics.&#x0D; Results: There were 277 respondents, comprising 93 teachers, 77 drivers, and 107 mechanics. The response rate was 95.1%. Seventy-two (77.4%) teachers, 56 (72.7%) drivers and 101 (94.4%) mechanics use herbal medicine for infectious diseases while 57 (61.3%) teachers, 20 (26.0%) drivers and 83 (77.6%) use herbal medicine for non-infectious diseases. Assessment of SEF shows that a significant number (p=0.04) of participants were encouraged by friends to use herbal medicines while 63 (67.7%) teachers, 57 (74.0%) drivers, and 84 (78.5%) mechanics preferred herbal medicine to hospital management because it is affordable. Assessment of HHI shows 81 (75.7%) mechanics are aware of HHI, whereas 56 (72.7%) drivers and 69 (74.2%) teachers are not. Similarly, majority of the teachers (81, 87.1%) and drivers (47, 61.0%) were not aware of the possible occurrence of HDI while a significant (p=0.03) number (76, 71.0%) of the mechanics were aware.&#x0D; Conclusion: The respondents’ awareness of herb-herb and herb-drug interactions was poor. Public awareness program on the potential implications and health impact of herb-herb and herb-drug interactions is highly essential.

Preclinical pharmacokinetics and herb-drug interaction studies of atorvastatin co-administered with the herbal slimming products

Herbal slimming products (HSPs) contain multiple herbs used in weight loss. Phytoconstituents of several plant extracts show the inhibitory effects on the drug-metabolizing enzymes causing interaction when taken with other drugs. Atorvastatin (ATS) is used in the treatment of hyperlipidemia. This study aimed to investigate the effect of HSPs on the pharmacokinetics and pharmacodynamics of ATS. ATS (10 mg/Kg) was administered alone or in combination with HSP1 (200 mg/Kg)/ HSP2 (165 mg/Kg) orally in the SD rats for pharmacokinetics study. Hyperlipidemia was induced in Golden Syrian Hamster by feeding HFD (60% kcal). Furthermore, biochemical levels in serum, ROS, gene expression and lipid accumulation levels were examined in hamster liver tissue. HSPs have significantly enhanced the permeability and inhibited the metabolism of ATS by inhibiting the CYP3A4 isoenzyme confirmed by in vitro assay. Co-administration of HSPs with ATS enhanced the relative bioavailability of ATS.Concomitant administration of HSPs with ATS has significantly reduced the fat content, inflammatory cytokines, TG, VLDL, LDL levels, tissue MDA level, HMGCR and SREBP1c mRNA expression levels, lipid accumulation as well as collagen content and has increased the serum HDL level as well as tissue SOD, CAT, GHS and mRNA expression levels of LXRα and CYP7A1. The aforementioned outcomes indicated that coadministration of HSPs with ATS may lead to herb-drug interaction. Therefore, precaution should be taken and dose adjustment is required when administered simultaneously.

Perceptions of drug-herbal interactions among Saudi Arabian individuals: An exploratory study

Perceptions of drug-herbal interactions among Saudi Arabian individuals: An exploratory study

Network pharmacology and bioinformatics based investigation of Phyllanthus fraternus: herb-drug interaction study

Phyllanthus fraternus (PF), a plant from the Euphorbiaceae family, is used extensively in ayurvedic formulations for its significant medicinal properties. When PF is administered alongside conventional drugs, there could be potential herb-drug interactions between the active compounds and the genes involved in drug transport and metabolism. Hence, this study was designed to investigate potential herb-drug interactions, focusing on elucidating their functional and pharmacological mechanisms, using an integrated approach of metabolite profiling and network pharmacology. We utilized LC-MS to generate metabolite profiling of PF and network pharmacology for predicting key targets and pathways. This comprehensive analysis involved the construction of networks illustrating the relationships among compounds, targets, and pathways and the exploration of protein-protein interactions and protein-ligand interactions. In this study, a total of 79 compounds were identified in LC-MS, such as alkaloids, steroids, saponins, flavonoids, lignans, phenolic acids, tannins, terpenoids, and fatty acids. The identified compound’s physicochemical properties were predicted using SwissADME. Network analysis predicted 1076 PF-related genes and 1497 genes associated with drug transport and metabolism, identifying 417 overlapping genes, including 51 related to drug transport and metabolism. Based on the degree of interaction the hub targets like ABCB1, CYP1A1, CYP1A2, CYP2C9, and CYP3A4 were identified. In the compound-target-pathway network, 2,4-bis(1,1-dimethyl ethyl)-phenol; 5-Methoxy-N-[(5-Methylpyridin-2-yl) sulfonyl]-1h-Indole-2-Carboxamide; and E,E,Z-1,3,12-Nonadecatriene-5,14-diol possessed more interactions with the targets. This study helps identify bioactive compounds, essential targets, and pathways potentially implicated in these interactions, laying the foundation for future studies (in vitro and in vivo) to verify their potential to explore their clinical implications.Communicated by Ramaswamy H. Sarma

Evaluation of pharmacological and pharmacokinetic herb-drug interaction between irinotecan hydrochloride injection and Kangai injection in colorectal tumor-bearing mice and healthy rats

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anti-colorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited pre-clinical evidence and safety concerns. This study aimed to determine the pre-clinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration.Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS.Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p &amp;lt; 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 μg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 μg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair.Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration.

Natural Product – Drug Interactions and Their Evaluation Using a Caco-2 Cell Culture Model

Natural products, such as herbal medicinal products, food supplements, and functional food, are widely used to support well-being and for promoting health. In general, the effects of using these products are desired and beneficial, but unexpected adverse effects might also occur, especially when natural products are used with medication. Consumers do not often even know that they are exposed to bioactive compounds that might interact with the body and have effects on their well-being. One of the objectives of the World Health Organization is to promote herb–drug interaction monitoring, and it is important to know how marketed preparations and compounds from common foods interact when they are absorbed. In this review, we describe how a Caco-2 cell absorption model has been used to study how natural products, such as flaxseed, rapeseed, purple loosestrife, pine, echinacea, certain berries and herbs, anthranoid laxatives, and traditional medicinal plants, affect the absorption of co-administered drugs. We discuss the types of interactions and adverse effects that might occur and their possible reasons. Overall, we conclude that the Caco-2 cell absorption model is a useful tool for studying the absorption of natural products with drugs; and that to enable the safe use of natural products with medicines, concomitant use should be studied.

Concept of Drug Metabolism and Pharmacokinetics with Special Focus on Herbal-Drug Interaction

The study of how xenobiotics undergo the process of absorption, distribution, metabolism, and excretion (ADME) is conceptualized as pharmacokinetics. An understanding therefore of the PK properties is crucial and plays an important contribution in the drug discovery and development of new chemical entities. Drug metabolism is linked to the metabolic breakdown of drugs (xenobiotic metabolism) by enzyme or living organisms. The pathway involved in this process can lead to the bio-transformations that occurs in most living organisms. The drug metabolic action facilitates the detoxification process except in special circumstances where the metabolites (break down products) can lead to toxic effects. Under such circumstances the study of drug metabolism is termed as pharmacokinetics, which constitutes an important discipline as a branch of pharmacology. Herbal natural products have been used to prevent and treat diseases worldwide since the creation of mankind. However, the efficacy, safety and quality of herbal bioactive metabolites depends on the multiple components absorbed in the body and their pharmacokinetics. This review attempts to give an insight into the concept of drug metabolism and pharmacokinetics with special consideration on PK drug-herbal interactions, mechanisms, metabolizing enzymes involved and transporters implicated in the determination of the PK of xenobiotics.

Integrated traditional herbal medicine in the treatment of gastrointestinal disorder: the pattern of use and the knowledge of safety among the Eastern Region Saudi population

BackgroundHerbal medicine is commonly integrated with conventional medicine in Saudi Arabia, especially for the management of digestive disorders. However, the majority of Saudis use herbal remedies without prior consultation with a physician, which raises concerns about their appropriate and safe use. The aim of this study was to assess the level of awareness among the Saudi population regarding the proper utilization and potential adverse effects of frequently used herbs for the treatment of gastrointestinal (GI) diseases.MethodsA cross-sectional survey was conducted in Saudi Arabia from January to March 2021. An electronic self-administered questionnaire was distributed.ResultsA total of 543 participants from different age groups, educational levels, and cities across Saudi Arabia completed the study questionnaire. The most commonly used herbs at home by the participants were: myrrh, parsley, black seed, chamomile, mint, anise, clove, and green tea. 57.7% of the participants perceived herbs as safer than conventional medicines; 27.3% reported that using herbal remedies over conventional medicine was a family tradition, and 21.4% used herbs because they were cheaper than conventional medicines.ConclusionHerbal remedies, including myrrh, parsley, blackseed, chamomile, mint, and anise, are commonly employed for the treatment of gastrointestinal disorders in Saudi Arabia. However, the knowledge level of participants regarding potential side effects and drug-herb interactions was found to be deficient. As such, there is a pressing need for educational campaigns and community awareness programs to elucidate the proper usage of herbal remedies and to caution against their potential adverse effects.

Signal Detection and Assessment of Herb-Drug Interactions: Saudi Food and Drug Authority Experience.

Numerous investigations on herbal medicine that have been undertaken in the past several years demonstrate the general acceptance of its safety. The Saudi Food and Drug Authority (SFDA) established the Herb-Drug Interaction (HDI) project to detect and assess potential HDIs to ensure safety. The aim is to detect safety signals and assess them based on available evidence. First, SFDA-registered herbal products (n=30) were selected and prioritized based on commonly used herbs. Second, reported potential HDIs were retrieved from the World Health Organization global database of individual case safety reports (VigiBase), AdisInsight®, and the Natural Medicines database. We excluded drugs non-registered by SFDA and labeled interactions in the product information of SFDA, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA). Finally, a comprehensive evaluation of potential HDIs was carried out using several evidence sources: literature, global cases, local cases, and other relevant documents. The Drug Interaction Probability Scale (DIPS) scale was used to assess the probability of a causal relationship between the interacting herb and drug and the event. The search yielded 566 potential signals, and 41 had published evidence and were referred for assessment. The assessment results using DIPS were: 22 possible (53.6 %), 7 probable (17%), and 12 doubtful (29.2%) interactions. The recommendation was to include probable HDIs in the product information, including turmeric-tacrolimus, etoposide-Echinacea, Ginkgo biloba-ibuprofen, green tea-warfarin, and licorice-thiazides interactions. The HDI project assessed the screening and identification of potential HDIs. The action plan of this project can be used in post-marketing activities to identify potential drug interactions.

Clinical Relevance of Drug Interactions in People Living with Human Immunodeficiency Virus on Antiretroviral Therapy-Update 2022: Systematic Review.

The clinical outcomes of antiretroviral drugs may be modified through drug interactions; thus, it is important to update the drug interactions in people living with HIV (PLHIV). To update clinically relevant drug interactions in PLHIV on antiretroviral therapy with novel drug interactions published from 2017 to 2022. A systematic review in Medline/PubMed database from July 2017 to December 2022 using the Mesh terms antiretroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full-text access were retrieved. The clinical relevance of drug interactions was grouped into five levels according to the gravity and probability of occurrence. A total of 366 articles were identified, with 219 (including 87 citation lists) were included, which allowed for the identification of 471 drug interaction pairs; among them, 291 were systematically reported for the first time. In total 42 (14.4%) and 137 (47.1%) were level one and two, respectively, and 233 (80.1%) pairs were explained with the pharmacokinetic mechanism. Among these 291 pairs, protease inhibitors (PIs) and ritonavir/cobicistat-boosted PIs, as well as integrase strand transfer inhibitors (InSTIs), with 70 (24.1%) and 65 (22.3%) drug interaction pairs of levels one and two, respectively, were more frequent. In PLHIV on antiretroviral therapy, we identify 291 drug interaction pairs systematically reported for the first time, with 179 (61.5%) being assessed as clinically relevant (levels one and two). The pharmacokinetic mechanism was the most frequently identified. PIs, ritonavir/cobicistat-boosted PIs, and InSTIs were the antiretroviral groups with the highest number of clinically relevant drug interaction pairs (levels one and two).

CYP2C9 mediates the herb-drug interaction of curcumin with naproxen in rats

Both curcumin and naproxen possess the activity of pain relief, which makes it possible to co-administrate these drugs in the same prescription. This study aimed to assess the potential pharmacokinetic interaction of naproxen with curcumin in rats. Sprague-Dawley (SD) rats were orally administrated with naproxen (10 mg/kg body weight) and curcumin (10 or 20 mg/kg, body weight) synchronously or successively with a single administration of naproxen as the control group. The plasma concentration of naproxen was analyzed with liquid chromatography tandem mass spectrometry and the plasma concentration-time curve was established to obtain the pharmacokinetic parameters. In vitro, the metabolic stability of naproxen and the activity of CYP2C9 was assessed in rat liver microsome to reveal the potential mechanism. Both synchronous and successive co-administration of naproxen and curcumin induced increased maximum concentration (Cmax), area under the curve (AUC0-t), half-life (t1/2) and reduced clearance rate (CLF) of naproxen in rats, and the effect of curcumin was enhanced with its increasing concentration. In vitro, curcumin (10 and 20 mg/kg) was found to enhance the metabolic stability of naproxen (half-life from 29.7 ± 1.34 to 41.8 ± 5.07 and 46.9 ± 3.33 min) and significantly inhibited the activity of CYP2C9 with the IC50 of 16.36 μmol/L (P &lt; 0.05). A combination of naproxen and curcumin would induce pharmacokinetic interaction, which increased the systemic exposure of naproxen. The concentration-dependent inhibition of CYP2C9 by curcumin was the potential mechanism underlying the drug-herb interaction.