Tolmetin Sodium is a non-steroidal anti-inflammatory drug.
Pharmacokinetics
Tolmetin sodium is rapidly and almost completely absorbed on oral administration, with peak plasma levels being
attained within the first hour of administration. It has a relatively short plasma half-life of approximately 1 hour
because of extensive first-pass metabolism, involving hydroxylation of the p-methyl group to the primary alcohol,
which is subsequently oxidized to the dicarboxylic acid.
Clinical Use
Tolmetin is synthesized straightforwardly from 1-methylpyrrole. It was introduced in the United States in 1976 and like other NSAIDs, inhibits prostaglandin biosynthesis. Tolmetin, however, also inhibits polymorph migration and
decreases capillary permeability. Its anti-inflammatory activity, as measured in the carrageenan-induced rat paw
edema and cotton pellet granuloma assays, is intermediate between those of phenylbutazone and indomethacin.
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The most frequently adverse reactions are those involving the GI tract (e.g., abdominal pain, discomfort, and nausea)
but appear to be less than those observed with aspirin. The CNS effects (e.g., dizziness and drowsiness) also are
observed. Few cases of overdosage have been reported, but in such cases, recommended treatment includes
elimination of the drug from the GI tract by emesis or gastric lavage and elimination of the acidic drug from the
circulatory system by enhancing alkalinization of the urine with sodium bicarbonate.
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This metabolite is inactive in standard in vivo
anti-inflammatory assays. The free acid (pKa = 3.5) is highly bound to plasma proteins (99%), and excretion of
tolmetin and its metabolites occurs primarily in the urine.Approximately 15 to 20% of an administered dose is excreted unchanged and 10% as the glucuronide conjugate of
the parent drug. Conjugates of the dicarboxylic acid metabolite account for the majority of the remaining administered
drug.
