Abstract 229: Correlation of in vitro Studies and Human Drug Interaction Studies with Gemcabene

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Margaret McShane ◽  
Louis Radulovic ◽  
Charles L Bisgaier
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Multiple Dose ◽  
Drug Reactions ◽  
Open Label ◽  
Transport Pathways ◽  
Dose Study

Background: Gemcabene is a novel lipid-regulating compound being developed as an adjunct to diet and statin therapy for dyslipidemia treatment. Patients with dyslipidemia typically take many medications often including statins and it is essential to understand potential risk of drug-drug interactions (DDI) to minimize the risk of adverse drug reactions. In the best circumstances, drugs entering the market will provide metabolic or transport pathways that do not interfere with commonly co-administered drugs. The current studies provide the analysis of potential drug interactions with gemcabene both in vitro and in vivo . Methods: Caco-2 cells were used to assess the potential P-gp substrate and inhibitor interaction and the major drug-metabolizing CYP450 isozymes and FMO-3 were used to assess the potential CYP450 and FM0-3 metabolism interaction. The results from the in vitro P-gp and CYP450 studies was correlated with the results of three DDI clinical studies with digoxin, atorvastatin and simvastatin. Results: In an open-label, multiple-dose study in 12 healthy subjects, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of digoxin (0.25 mg). Specifically, the 90% confidence interval for digoxin AUC (0-24) ratios were within the 80% to 125% range, thus confirming the in vitro results of no DDI with a P-gp substrate. In two open-label, multiple-dose studies in healthy volunteers, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of atorvastatin (80 mg) or simvastatin (80 mg) thus confirming the in vitro results of no DDI with CYP450 (see Figure below). Conclusion: These results suggest gemcabene is unlikely to elicit a metabolic (i.e., CYP450 or FMO3) or P-gp-mediated drug interaction. Gemcabene (900 mg) was well-tolerated in combination with highest dose of atorvastatin and simvastatin. Clinical Implications: Understanding potential for drug interactions minimizes the risk of adverse drug reactions.

Oral Terbinafine: A New Antifungal Agent

1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Case Reports ◽  
Current Standard ◽  
Open Label ◽  
Double Blind ◽  
Pathogenic Yeast

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

scholarly journals Potential clinically significant life-threatening drug–drug interactions of lopinavir and ritonavir used in the treatment of COVID-19

2020 ◽  
Vol 1 ◽  
Author(s):  
Mohitosh Biswas
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Drug Reactions ◽  
Significant Life ◽  
Life Threatening ◽  
Clinically Significant ◽  
Prescribing Information

AbstractPotential clinically significant life-threatening drug–drug interactions (DDIs) of lopinavir (LPV) and ritonavir (RTV) used in the treatment of COVID-19 is not systematically reviewed. It was aimed to identify severe DDI pairs of LPV/RTV from international resources predicted to cause life-threatening adverse drug reactions (ADRs). Severe DDI pairs predicted to cause life-threatening ADRs were identified from the FDA and Liverpool COVID-19 prescribing information of LPV/RTV. In total, 62 severe DDI pairs were identified from the FDA and Liverpool COVID-19 resources predicted to cause life-threatening ADRs in patients with COVID-19. Of these, seven unique DDI pairs (11.3%; 95% CI 3%–19%) were identified from the FDA only whereas 45 unique DDI pairs (72.6%; 95% CI 61%–84%) were identified from the Liverpool COVID-19 drug interactions resource. Of interest, only 10 DDI pairs (16.1%; 95% CI 7%–25%) were recognized by both of these drug interaction resources. Clinicians should not entirely rely on any individual DDI resource for checking life threatening ADRs of LPV/RTV in patients with COVID-19.

scholarly journals Predicting the Severity of Adverse Drug Reactions

2020 ◽  
pp. 605-609
Author(s):  
Ms Sushmitha ◽  
Ms. Sowmya ◽  
Sushma Rao
Keyword(s):  
Clinical Trials ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Clinical Outcomes ◽  
Adverse Drug Reactions ◽  
High Accuracy ◽  
Drug Reactions ◽  
Drug Mixtures ◽  
Literature Reviews ◽  
Area Unit

<p>Polypharmacy, co-prescribing multiple medication, is implausibly common and infrequently ends up in drug interactions that may have adverse facet effects. Currently, to help doctors in prescribing treatments, clinical call systems fireplace alerts once drug mixtures area unit prescribed that have glorious reactions. Those alerts area unit supported drug interaction severity stored in databases like Lexi-Interact. However, Lexi-Interact severity, that is predicated on clinical trials and literature reviews, doesn't embrace all drug interactions tho' there are several prescribed drug mixtures that haven’t been lined by literature. This paper is enforced by coaching a model that has comparatively high accuracy and recall with glorious Lexi-Interact severity values, the goal would be to check it on drug interactions with glorious severity. Specifically, a drug combine would have a foreseen severity so a panel of clinical pharmacists, people acquainted with clinical outcomes of drug interactions, would rate the validity of that foreseen severity. We intend to realize such reactive medication and report them to the doctors.</p>

scholarly journals Kajian Adverse Drug Reactions Terkait Interaksi Obat di Bangsal Rawat Inap Rumah Sakit Akademik UGM

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Fivy Kurniawati ◽  
Nanang Munif Yasin ◽  
Amila Dina ◽  
Sanses Atana ◽  
Sarah Nabila Hakim
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Teaching Hospital ◽  
Clinical Problem ◽  
Cross Sectional Study ◽  
Potential Drug ◽  
Drug Reactions ◽  
Cross Sectional ◽  
Prolonged Length

Adverse Drug Reactions (ADRs) is one of the causes of patient’s prolonged length of stay in the hospital and drug interactions can be included as one of the causes of the cause of ADRs. ADR related to drug interactions is a clinical problem that requires proper prevention. This study aimed to identify potential drug interactions also identify adverse drug reactions (ADRs) related to drug interactions in hospitalized patients at Universitas Gadjah Mada Teaching Hospital. This cross-sectional study used retrospective data collection through patient’s medical records from January to June 2018. Patients included in this study were all patients who received therapy more than two kind of drugs simultaneously treated in hospital wards of Universitas Gadjah Mada Teaching Hospital, Yogyakarta, Indonesia. The data collected were then analyzed descriptively. Drug interactions were analyzed using Drug Interaction Facts 2012 and Stockley. ADRs were analyzed by monitoring documented effects of patients with potential drug interaction. There were 115 of 362 patients (31.8%) with potential drug interactions. The total numbers of potential interactions that occur were 182 interactions. The most potential type of interaction was the interaction with moderate severity, with 115 interactions (63.2%). The majority of drug interactions occur through unknown mechanisms (54.4%). Actual ADR occurs in 3.3% patients who were 2 pediatric patients and 4 geriatric patients. This study can be a reference for drug interactions and ADRs as well as guide for pharmacist and healthcare in providing the right medication.

Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China

2020 ◽  
Vol 21 ◽  
Author(s):  
Xuan Yu ◽  
Zixuan Chu ◽  
Jian Li ◽  
Rongrong He ◽  
Yaya Wang ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Penicillin G ◽  
Literature Mining ◽  
Human Pharmacokinetics ◽  
P450 Enzyme ◽  
Drug Drug Interaction ◽  
Pharmacokinetic Drug ◽  
Sepsis Care

Background: Many antibiotics have a high potential for having an interaction with drugs, as perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients. Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature mining was conducted to obtain human pharmacokinetics/dispositions of the antibiotics, their interactions with drug metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index > 0.1 for inhibition or a treated-cell/untreated-cell ratio of enzyme activity being > 2 for induction. Results: The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized. Conclusion: Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three lipophilic antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no reported clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibacterials (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.

Review on the Clinical Pharmacology of Hydroxychloroquine Sulfate for the Treatment of COVID-19

2020 ◽  
Vol 21 (6) ◽  
pp. 427-435 ◽  
Author(s):  
Cheng Cui ◽  
Siqi Tu ◽  
Valerie Sia Jie En ◽  
Xiaobei Li ◽  
Xueting Yao ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Clinical Efficacy ◽  
Relevant Literature ◽  
The United States ◽  
Efficacy And Safety ◽  
Open Label ◽  
Infected People ◽  
Treatment Regimens ◽  
Therapeutic Drugs

Background: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is greatly increasing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, so it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publications on hydroxychloroquine (HCQ) with anti- SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. Methods: We used the keyword "hydroxychloroquine" to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, its clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions to extract and organize information. Results: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposureresponse relationship and precautions and drug interactions of HCQ, and summarizes dosage recommendations for HCQ sulfate. Conclusion: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.

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