Metabolism of Some Kava Pyrones in the Rat

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Abstract
The metabolism in rats of several kava pyrones from Piper methysticum Forst. was studied. The compounds were the 5,6-dihydro-.alpha.-pyrones, dihydrokawain, kawain and methysticin, and the .alpha.-pyrones, 7,8-dihydroyangonin and yangonin. Approximately 1/2 the dose (400 mg/kg, orally) of dihydrokawain was found in the urine in 48 h. About 2/3 of this was hydroxylated metabolites (3 mono- and 3 dihydroxylated derivatives), of which p-hydroxydihydrokawain was the most abundant. The remaining 1/3 consisted of metabolites formed by scission of the 5,6-dihydro-.alpha.-pyrone ring and included hippuric acid (9-13% dose). Lower amounts of urinary metabolites were excreted when kawain was given but both hydroxylated and ring-opened products were formed. Methysticin gave rise to only small amounts of 2 urinary metabolites formed by demethylenation of the methylenedioxyphenyl moiety. Urinary metabolites of the .alpha.-pyrones, 7,8-dihydroxyangonin and yangonin, were formed via O-demethylation. No ring-opened products were detected. These lipophilic kava pyrones have extremely low solubility in water, which would be expected to reduce their absorption rates and appears to be responsible for the variable and low extent of metabolism observed.