Due to the poor bioavailability of curcumin, no clinical trials have progressed beyond the Phase I stage.

Early experiments indicated that curcumin undergoes transformation during absorption from the intestine. When administered orally to rats in a dose of 1 g/kg, curcumin was excreted in the feces to about 75%, while negligible amounts of curcumin appeared in the urine¹. Measurements of blood plasma levels and biliary excretion showed that curcumin was poorly absorbed from the gut. No apparent toxic effects were seen after doses of up to 5 g/kg. When intravenously injected or when added to the perfusate of the isolated liver, curcumin was actively transported into bile, against concentration gradients of several hundred times. The major part of the absorbed drug was, however, metabolized. In suspensions of isolated hepatocytes or liver microsomes 90% of the added curcumin was metabolized within 30 min. The authors concluded that in view of the poor absorption, rapid metabolism and excretion of curcumin, it is unlikely that substantial concentrations of curcumin occur in the body after ingestion. This study, which appeared as early as 1978, appears to summarize our current understanding of the metabolic fate of curcumin in vivo.

Later studies have more or less confirmed these findings. Oral and intraperitoneal doses of [3H] curcumin led to the fecal excretion of most of the radioactivity². Intravenous and intraperitoneal doses of [3H] curcumin were well excreted in the bile of cannulated rats. The major biliary metabolites were glucuronides of tetrahydrocurcumin and hexahydrocurcumin. The major route of elimination of the label was the feces; the urinary excretion of the label was very low regardless of the dose; however, its metabolites, namely, glucuronide and sulfate, were present³.