Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans

Halwes, Michael E.; Steinbach-Rankins, Jill M.; Frieboes, Hermann B.

doi:10.1016/j.ejps.2016.08.037

Cited by 7 publications

(20 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results showed that there were no differences in the concentration of DPV between film and gel in plasma, cervical tissues and cervico‐vaginal fluid. In terms of pharmacokinetics and antiviral effect, both film and gel DPV executed similar performance . In terms of concurrent use of DPV with other administration, the use of vaginal ring would not decrease the effectiveness of hormonal contraceptives in women who administer hormonal contraceptives and DPV vaginal ring simultaneously…”

Section: Non‐nucleoside Reverse Transcriptase Inhibitormentioning

confidence: 96%

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Yap

Xin

Tan

et al. 2019

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP. Key findings Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class. Summary Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.HIV and pre-exposure prophylaxis Pui Khee Yap et al.

show abstract

Section: Non‐nucleoside Reverse Transcriptase Inhibitormentioning

confidence: 96%

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Yap

Xin

Tan

et al. 2019

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…Where F represents the dose fraction absorbed, with dose D, k representing absorption, K representing elimination rate constants and V representing the apparent volume of distribution (33)(34)(35)(36)(37). This compartmental model without lag demonstrates the slow release behaviour of the copolymeric formulations, explaining the time-delayed response for the transition in pH for desired release kinetics.…”

Section: Pharmacokinetic Modelling Using Non-compartmental and Compartmental Analysismentioning

confidence: 98%

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

et al. 2017

View full text Add to dashboard Cite

A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-β) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-β and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-β peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.

show abstract

“…The gel is a suspension of inorganic or organic particles interpenetrated by an aqueous or nonaqueous liquid (Antimisiaris & Mourtas, 2015; Garg et al, 2010; Rohan et al, 2014). Its high lubrication capacity and wide acceptance contribute to it being the most widely studied formulation as vaginal microbicide (Al‐Khouja et al, 2020; Bunge et al, 2018; Delany‐Moretlwe et al, 2018; Halwes et al, 2016). The tablets are polymers that gel in the presence of vaginal fluids and overcome stability concerns related to gels (Antimisiaris & Mourtas, 2015; Garg et al, 2010; Rohan et al, 2014).…”

Section: Vaginal Formulations: Development and Characterizationmentioning

confidence: 99%

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

Rodriguez-Izquierdo

Sepúlveda‐Crespo

Lasso³

et al. 2022

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers

show abstract

Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans

Cited by 7 publications

References 33 publications

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

Contact Info

Product

Resources

About