efavirenz

The elevated concentration of macrophage inflammatory protein-1 alpha was the only marker indicative of elevated levels of inflammation associated with DTG-based treatment. The transition from EFV- to DTG-based regimens therefore appears to be of potential benefit with metabolic and inflammatory markers, as well as those associated with cardiovascular disease and other chronic non-AIDS-related diseases, reaching levels similar to those observed in individuals not living with HIV.

In addition to its anti-cancer properties, efavirenz has the advantage of being a well-established and relatively inexpensive medication with a favorable safety profile. If proven effective, efavirenz could offer a cost-effective therapeutic option, which is an intriguing direction that warrants further investigation.

Previous studies have shown that SHR6390 in combination with rifampicin, a potent inducer of CYP3A4, significantly reduces exposure levels. It is recommended to avoid concomitant administration of moderate inducers of CYP3A4 during treatment with SHR6390. http://www.chinadrugtrials.org.cn/index.html, CTR20211571/ https://classic.clinicaltrials.gov, NCT04973020.

Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0-72.2 and 51.1% (95% CI 34.0-76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.

P1, N=34, Completed, Shenzhen TargetRx, Inc. | Recruiting --> Completed

The purpose of this study was to develop and validate a physiologically based pharmacokinetic (PBPK) model combined with an EGFR occupancy (EO) model for osimertinib (OSI) to predict plasma trough concentration (Ctrough) and the intracranial time-course of EGFR (T790M and L858R mutants) engagement in patient populations. When used concomitantly with CYP enzyme perpetrators, the PBPK-EO model suggested appropriate dosing regimens of 80 mg OD with fluvoxamine (FLUV) itraconazole (ITR) or fluvoxamine (FLUC) for co-administration and an increase to 160 mg OD with rifampicin (RIF) or efavirenz (EFA). In conclusion, the PBPK-EO model has been shown to be capable of simulating the pharmacokinetic concentration-time profiles and the time-course of EGFR engagement for OSI, as well as determining the optimum dosing in various clinical situations.

P1, N=26, Completed, Pfizer | N=13 --> 26

P1, N=32, Recruiting, Shenzhen TargetRx, Inc. | Not yet recruiting --> Recruiting

P1, N=32, Not yet recruiting, Shenzhen TargetRx, Inc.

Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans...Simulations using the developed model predicted that moderate CYP3A inhibitors (e.g., verapamil and diltiazem) may increase brigatinib AUC by ~40%, whereas moderate CYP3A inducers (e.g., efavirenz) may decrease brigatinib AUC by ~50%. Simulations of potential transporter-mediated DDIs predicted that brigatinib may increase systemic exposures (AUC ) of P-gp substrates (e.g., digoxin and dabigatran) by 15%-43% and MATE1 substrates (e.g., metformin) by up to 29%; however, negligible effects were predicted on BCRP-mediated efflux and OCT1-mediated uptake. The PBPK analysis results informed dosing recommendations for patients receiving moderate CYP3A inhibitors (40% brigatinib dose reduction) or inducers (up to 100% increase in brigatinib dose) during treatment, as reflected in the brigatinib prescribing information.

The role of CYP3A4 in the clearance of glasdegib has been confirmed with clinical drug-drug interaction (DDI) studies following co-administration of glasdegib with strong CYP3A4 inhibitor ketoconazole and strong inducer rifampin. To evaluate the potential drug interactions with CYP3A4 modulators, co-administration of glasdegib with a moderate CYP3A4 inducer, efavirenz, was evaluated using physiologically based pharmacokinetic (PBPK) modeling using the Simcyp simulator...PBPK modeling predicted a glasdegib area under the concentration-time curve ratio of 0.45 and maximum plasma concentration ratio of 0.75 following co-administration with efavirenz. The PBPK results, in lieu of a formal clinical study, informed the drug label with the recommendation to double the clinical dose of glasdegib when administered in conjunction with a moderate CYP3A4 inducer, followed by resumption of the original dose 7 days post discontinuation.

Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.

Oral administration with M + E + F combination for 3 weeks caused dramatic reductions in tumor volume and weight in HCT116 xenograft model of nude mice when compared with untreated ones. Our results suggest that M + E + F have profound anticancer activity both in vitro and in vivo via a cancer cell-specific ROS amplification (CASRA) through ROS-induced DNA damage, apoptosis, autophagy, and necroptosis.

The physiologically based pharmacokinetic model predicted that a moderate CYP3A4 inhibitor and a moderate CYP3A inducer would produce modest increases and decreases, respectively, in pexidartinib exposure. These results provide a basis for pexidartinib dosing recommendations when administered concomitantly with drugs with drug-drug interaction potential, including dose adjustments when concomitant administration cannot be avoided.

P2, N=30, Recruiting, Fudan University | N=20 --> 30

P2, N=20, Recruiting, Fudan University | Initiation date: Apr 2022 --> Jun 2022

The aim of this study was to investigate the effects of the NNRTIs efavirenz, rilpivirine and doravirine, and the NRTIs tenofovir disoproxil fumarate and emtricitabine, on beta-cell function and survival while suggesting potential cellular and molecular mechanism(s). The deleterious effects observed in beta-cells exposed to efavirenz or rilpivirine may be, at least partially, mediated by oxidative stress and mitochondrial toxicity. These findings provide potential mechanism(s) by which efavirenz and rilpivirine may contribute to the pathogenesis of T2DM and the progression of T2DM to insulin dependency in HIV-infected type 2 diabetics.

Efavirenz caused upregulation of several CSC-related genes as well as miR-21, a CSC marker and miR-182, a CSC suppressor gene. We conclude that Efavirenz alters the phenotype and expression of key genes in breast CSCs, which has important potential therapeutic implications.

We followed those initiating ART after 1 Jan 2004 with a nucleos(t)ide backbone of either abacavir/lamivudine or tenofovir/emtricitabine and a modern third (anchor) drug until a first ESLD event, death, end of a cohort's ESLD validation period, loss to follow up or 31 Dec 2015...Both backbones and efavirenz show no signs of liver toxicity. Of the nine anchor drugs, boosted atazanavir and darunavir have the strongest signals... We show how new user cohort designs can be used to detect toxicity signals even with relatively few events. While modern ART poses less risk for ESLD than hepatitis coinfection, some drugs showed toxicity signals. Confirming whether these drugs contribute to ESLD risk requires designs that focus on causality

African Potato is mainly used as an immunostimulant. The exact mechanisms of action for all the pharmacological actions are unknown. More research is required to substantiate claims regarding beneficial effects. There are many research gaps that require investigation including pharmacokinetic interactions with conventional drugs, especially those used in HIV/AIDS.

Interestingly, the p53 signaling pathway was activated irrespective of the repressed ATM pathway in A549 cells as revealed by the Ingenuity Pathway Analysis (IPA). These EFV effects are similar to those of ionizing radiation and this suggests that EFV has anti-tumour properties.