Metabolism of ester local anesthetics is carried out by plasma cholinesterases (pseudocholinesterases) and is very rapid for procaine (half-life, 1–2 min), slower for cocaine, and very slow for tetracaine). The amides are metabolized in the liver, in part by cytochrome P450 isozymes. The half-lives of lidocaine and prilocaine are approximately 1.5 h. Bupivacaine and ropivacaine are the longest-acting amide local anesthetics with half-lives of 3.5 and 4.2 h, respectively. Liver dysfunction may increase the elimination half-life of amide local anesthetics (and increase the risk of toxicity). Acidification of the urine promotes ionization of local anesthetics; the charged forms of such drugs are more rapidly excreted than nonionized forms.