Adults

Dosage varies greatly depending on the procedure, area to be anesthetized, vascularity of tissues, depth of anesthesia required, and individual patient tolerance. For epidural block: 15-30 mg (3-6 ml of 0.5% solution) as a test dose, followed by increments to a maximum single dose of 150-200 mg (30-40 ml) or 400 mg/24 hours.

Elderly

Reduced doses may be required, especially in debilitated patients, due to potential for reduced hepatic metabolism and renal excretion. Dosing should be individualized and initiated at the lower end of the dosing range.

Renal_impairment

Generally no specific dose adjustment needed for single-dose use, but caution advised with repeated doses due to potential accumulation of metabolites.

Onset

Typically 2-10 minutes for epidural anesthesia, 5-15 minutes for peripheral nerve blocks, 10-20 minutes for caudal block.

Excretion

Metabolites and a small percentage of unchanged drug (approximately 5-6%) are excreted via the kidneys.

Half life

Plasma elimination half-life is approximately 1.5-5.5 hours in adults, longer in neonates and patients with hepatic impairment.

Absorption

Systemic absorption depends on the route of administration, dose, vascularity of the injection site, and presence of vasoconstrictor. Peak plasma levels usually occur within 30-45 minutes following epidural administration.

Metabolism

Primarily metabolized in the liver by cytochrome P450 enzymes (CYP1A2 and CYP3A4) via N-dealkylation to form pipecolylxylidine (PPX) and 2,6-xylidine.

Other local anesthetics

Increased risk of systemic toxicity if used concurrently or sequentially, especially with higher doses.

Alpha-adrenergic blockers

May enhance systemic absorption due to vasodilation.

Antiarrhythmics (e.g., mexiletine, amiodarone)

Concurrent use may increase the risk of cardiac toxicity due to additive effects on cardiac conduction.

CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine)

May increase bupivacaine plasma levels, increasing toxicity risk.