Book Text

Biotransformation and Excretion

The pattern of metabolism of local anesthetics varies according to their chemical classification. Ester, or procaine-like, drugs undergo hydrolysis in plasma by pseudocholinesterase enzymes. Chloroprocaine has the fastest rate, 4.7 mol/mL/hr, versus rates of 1.1 mol/mL/hr for procaine and 0.3 mol/mL/hr for tetracaine. ^[107] ^[108]

The aminoamide drugs undergo enzymatic degradation primarily in the liver. Lidocaine is metabolized somewhat more rapidly than mepivacaine,^[108] and bupivacaine is metabolized more slowly than either lidocaine or mepivacaine. ^[109] Some degradation of the amide-type compounds may take place in tissues other than liver; in particular, the metabolism of lidocaine is discussed in detail elsewhere.^[108]

**TABLE 14-10** -- Pharmacokinetic properties of various amide local anesthetics
Agent	t_½α (min)	t_½β (min)	V_dss (L)	t_½γ (hr)	CI (L/min)
Prilocaine	0.5	5.0	261	1.5	2.84
Lidocaine	1.0	9.6	91	1.6	0.95
Mepivacaine	0.7	7.2	84	1.9	0.78
Bupivacaine	2.7	28.0	72	3.5	0.47
Etidocaine	2.2	19.0	133	2.6	1.22
CI, clearance; V_dss , volume of distribution at steady state.

Excretion of the metabolites of amide-type local anesthetics occurs through the kidney. Less than 5% of the unchanged drug is excreted by the kidney into urine.