Effect of lithium on gastric emptying and absorption of oral chlorpromazine.

A recent study suggested that low plasma levels (58-70 ng/ml) of chlorpromazine (CPZ) were achieved by patients concurrently taking lithium, despite ingestion of doses of CPZ (400-1000 MG) which ordinarily produce plasma levels of 100-300 ng/ml or more. We have studied this lithium-chlorpromazine interaction in rats. The plasma and brain levels of [14C]chlorpromazine (CPZ) after an oral dose (5 muCi) were significantly lower (p less than 0.005) in rats treated with lithium, whereas the percent of dose remaining in the stomach (24-30%) was significantly higher (p less than 0.001), than in matched controls. Gastric emptying was measured by [14C]polyethylene glycol and was shown to be inhibited significantly by oral and i.p. lithium. This inhibition of gastric emptying by lithium may be the major cause of the lower plasma levels of CPZ since diminution of plasma drug levels has been shown for L-dopa, chlorpromazine, sulfa drugs, and phenylbutazone in animals and man treated concomitantly with anticholinergics, which also diminish gastric motility.