Species Similarities and Differences in Pharmacokinetics and Distribution of Antiretroviral Drugs

Owen, Andrew; Curley, Paul

doi:10.1007/978-1-4939-1655-9_28

Cited by 5 publications

(4 citation statements)

References 115 publications

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“…Species differences in clearance would indicate that the formulations in humans may provide even greater exposure. In general, smaller species have a higher rate of clearance [ 39 ]. FTC specifically is renally cleared at a rate of 22.3 mL/kg/min in rats and 3.5 mL/kg/min in humans [ 31 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations

et al. 2023

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Long-acting injectable (LAI) formulations promise to deliver patient benefits by overcoming issues associated with non-adherence. A preclinical assessment of semi-solid prodrug nanoparticle (SSPN) LAI formulations of emtricitabine (FTC) is reported here. Pharmacokinetics over 28 days were assessed in Wistar rats, New Zealand white rabbits, and Balb/C mice following intramuscular injection. Two lead formulations were assessed for the prevention of an HIV infection in NSG-cmah−/− humanised mice to ensure antiviral activities were as anticipated according to the pharmacokinetics. Cmax was reached by 12, 48, and 24 h in rats, rabbits, and mice, respectively. Plasma concentrations were below the limit of detection (2 ng/mL) by 21 days in rats and rabbits, and 28 days in mice. Mice treated with SSPN formulations demonstrated undetectable viral loads (700 copies/mL detection limit), and HIV RNA remained undetectable 28 days post-infection in plasma, spleen, lung, and liver. The in vivo data presented here demonstrate that the combined prodrug/SSPN approach can provide a dramatically extended pharmacokinetic half-life across multiple preclinical species. Species differences in renal clearance of FTC mean that longer exposures are likely to be achievable in humans than in preclinical models.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations

et al. 2023

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“…Some in vitro models are beginning to be established that investigate all aspects of oral administration and the interaction of enzymes with the intestinal mucosa and epithelial cells. However, despite the advantages of using in vitro models, the current in vitro systems cannot completely replicate the complexities observed in vivo [36–40]. Therefore, it is necessary to study in vivo models.…”

Section: Simulating the Gastrointestinal Mucus Barriermentioning

confidence: 99%

Oral drug delivery with nanoparticles into the gastrointestinal mucosa

Liu¹,

Leng²,

Liu³

2020

Fundamemntal Clinical Pharma

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The oral route of protein and peptide drugs has been a popular method of drug delivery in recent years, although it is often a challenge to achieve effective drug release and minimize the barrier functions of the gastrointestinal tract. Gastrointestinal mucosa can capture and remove harmful substances; similarly, it can limit the absorption of drugs. Many drugs are effectively captured by the mucus and rapidly removed, making it difficult to control the release of drugs in the gastrointestinal tract. The use of drug carrier systems can overcome the mucosal barrier and significantly improve bioavailability. Nanoparticle drug carriers can protect the drug from degradation, transporting it to a predetermined location in the gastrointestinal tract to achieve more efficient and sustained drug delivery. It is becoming clearer that the characteristics of nanoparticles, such as particle size, charge, and hydrophobicity, are related to permeability of the mucosal barrier. This review focuses on the latest research progress of nanoparticles to penetrate the mucosal barrier, including the delivery methods of nanoparticles on the surface of gastrointestinal mucosa, and aims to summarize how successful oral nanoparticle delivery systems can overcome this biological barrier in the human body. In addition, the in vitro model based on gastrointestinal mucus is an important tool for drug research and development. Here, we discuss different types of drug delivery systems and their advantages and disadvantages in design and potential applications. Similarly, we reviewed and summarized various methods for evaluating oral nanoparticles in in vitro and in vivo models.

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“…Additionally, rodents have a significantly higher density of Peyer's patches in the intestine when compared to humans and this should be considered when optimising oral absorption via this pathway [113]. In addition to anatomical differences, there are important variances between species in the expression and/or activity of metabolic enzymes and transporters relevant to intestinal absorption [114][115][116][117].…”

Section: Limitations In Using In Vitro and In Vivo Models In Nanopartmentioning

confidence: 99%

The biological challenges and pharmacological opportunities of orally administered nanomedicine delivery

Moss

Curley

Kinvig

et al. 2017

Expert Review of Gastroenterology & Hepatology

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Nano-scale formulations are being developed to improve the delivery of orally administered medicines, and the interactions between nanoformulations and the gastrointestinal luminal, mucosal and epithelial environment is currently being investigated. The mucosal surface of the gastrointestinal tract is capable of trapping and eliminating large particles and pathogens as part of the natural defences of the body, it is becoming clearer that nanoformulation properties such as particle size, charge, and shape, as well as mucous properties such as viscoelasticity, thickness, density, and turn-over time are all relevant to these interactions. However, progress has been slow to utilise this information to produce effective mucous-penetrating particles. Areas covered: This review focuses on delivery method of nanomedicines both into and across the gastrointestinal mucosal surface, and aims to summarise the biological barriers that exist to successful oral nanomedicine delivery and how these barriers may be investigated and overcome. Expert commentary: Despite successes in the laboratory, no nanotechnology-enabled products are currently in clinical use which either specifically target the intestinal mucous surface or cross the epithelial barrier intact. New nanomedicine-based treatments of local diseases (intestinal cancer, inflammation, infection) and systemic diseases are advancing towards clinical use, and offer genuine opportunities to improve therapy.

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Species Similarities and Differences in Pharmacokinetics and Distribution of Antiretroviral Drugs

Cited by 5 publications

References 115 publications

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations

Oral drug delivery with nanoparticles into the gastrointestinal mucosa

The biological challenges and pharmacological opportunities of orally administered nanomedicine delivery

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