Liposomal Bupivacaine's Plausibility Fails to Translate

Local anesthetics (LAs) are commonly used for various applications in medical and dental procedures. Some of the common agents used are cocaine, lidocaine, and bupivacaine.
Cocaine is an ester of benzoic acid and methylecgogine. It is used to anesthetize and vasoconstrict locally. Currently, it is used primarily for topical applications. It is beneficial for surgeries on the upper respiratory tract, providing anesthesia and shrinking the mucosa. Cocaine in the form of cocaine hydrochloride is...

Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...

Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...

Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...

Intravenous regional anesthesia or the Bier block technique is used to anesthetize a specific limb or extremity. It uses exsanguinated or blood-drained vessels to transport local anesthetics or LAs to the peripheral nerve trunks. Lidocaine without vasoconstrictors like epinephrine is most commonly used for this technique. Other drugs used are prilocaine, ropivacaine, and chloroprocaine. Bupivacaine is not recommended for this technique due to its high cardiac toxicity.
One of the advantages of...

Drug distribution within the body is a complex process influenced by several factors, including perfusion rate, the rate at which the bloodstream transports drugs to tissue. This limitation becomes particularly significant when dealing with highly lipophilic drugs. In such cases, the rate at which the drug can move across membranes is crucial, and if the membrane is highly permeable to the drug, distribution becomes rate-limited by perfusion.
Perfusion rate-limited distribution relies on the...