microsurgical-skills-establishing-permanent-jugular-vein-cannulation

Microsurgical Skills of Establishing Permanent Jugular Vein Cannulation in Rats for Serial Blood Sampling of Orally Administered Drug

Blood sampling in small laboratory animals is necessary for pharmaceutical lead optimization but can cause great harm and stress to experimental animals, ...

Northwestern Polytechnical University

Drug dosing in clinical practice, which determines optimal efficacy, toxicity or ineffectiveness, is critical to patients' outcomes. However, many orally administered therapeutic drugs are susceptible to biotransformation by a group of important oxidative enzymes, known as cytochrome P450s (CYPs). In particular, CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions. This review explores the need for addressing intestinal CYP3A4 metabolism and investigates the opportunities to incorporate lipid-based oral drug delivery to enable precise dosing. A variety of lipid- and lipid-polymer hybrid-nanoparticles are highlighted to improve drug bioavailability. These drug carriers are designed to target different intestinal regions, including (1) local saturation or inhibition of CYP3A4 activity at duodenum and proximal jejunum; (2) CYP3A4 bypass via lymphatic absorption; (3) pH-responsive drug release or vitamin-B targeted cellular uptake in the distal intestine. Exploitation of lipidic nanosystems not only revives drugs removed from clinical practice due to serious drug-drug interactions, but also provide alternative approaches to reduce pharmacokinetic variability.

Ruimin Miao

Xi'an Key Laboratory of Stem Cell and Regenerative Medicine,
Institute of Medical Research,
Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research

Northwestern Polytechnical University

Microsurgical Skills of Establishing Permanent Jugular Vein Cannulation in Rats for Serial Blood Sampling of Orally Administered Drug

Ruimin Miao

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Xi'an Key Laboratory of Stem Cell and Regenerative Medicine,Institute of Medical Research,Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research

Northwestern Polytechnical University

Microsurgical Skills of Establishing Permanent Jugular Vein Cannulation in Rats for Serial Blood Sampling of Orally Administered Drug

Xi'an Key Laboratory of Stem Cell and Regenerative Medicine,
Institute of Medical Research,
Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research