Metabolism of some kava pyrones in the rat.
1. 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-dihyroyangonin and yangonin. 2. Approx. half the dose (400 mg/kg, p.o.) of dihydrokawain was found in the urine in 48 h. About two-thirds of this was hydroxylated metabolites (three mono- and three di-hydroxylated derivatives), of which p-hydroxydihydrokawain was the most abundant. The remaining third consisted of metabolites formed by scission of the 5,6-dihydro-alpha-pyrone ring and included hippuric acid (9--13% dose). 3. Lower amounts of urinary metabolites were excreted when kawain was given, but both hydroxylated and ring-opened products were formed. 4. Methysticin gave rise to only small amounts of two urinary metabolites formed by demethylenation of the methylenedioxyphenyl moiety. 5. Urinary metabolites of the alpha-pyrones, 7,8-dihydroxyangonin and yangonin, were formed via omicron-demethylation. No ring-opened products were detected. 6. 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.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002432:Cecum / Q000378:metabolism; D002849:Chromatography, Gas; D005243:Feces / Q000032:analysis; D007408:Intestinal Absorption; D008297:Male; D013058:Mass Spectrometry; D010945:Plants, Edible; D011714:Pyrans / Q000378:metabolism*; D011753:Pyrones / Q000378:metabolism* / Q000652:urine; D051381:Rats; D012995:Solubility
D011714:Pyrans; D011753:Pyrones