Saliva levels of trimethadione and its metabolite as an index of drug metabolizing activity in rats.
1. It was investigated in normal and liver-injured rats administered with trimethadione (TMO) as to whether concentrations of TMO in plasma are able to be predicted from the corresponding saliva levels. 2. The saliva/plasma (S/P)ratio of TMO was about 1, while its metabolite 5,5-dimethyl-2,4-oxazolidinedione (DMO) showed a S/P ratio of 0.65. 3. In normal rats, there was a high correlation between saliva and plasma concentration of TMO and DMO. (TMO: r=0.966, DMO: r=0.950). 4. In liver-injured pretreated rats with carbon tetrachloride, alpha-naphthyl isothiocyanate or D-galactosamine, there was a high correlation between the saliva DMO/TMO ratio and the plasma DMO/TMO ratio after oral administration of TMO (r=0.983 at 1 h, r=0.952 at 2 h). 5. The saliva DMO/TMO ratio, as well as the plasma DMO/TMO ratio, may be utilized as an index of drug-metabolizing activity of the liver.
D000818:Animals; D001711:Biotransformation; D006863:Hydrogen-Ion Concentration; D008297:Male; D010080:Oxazoles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012463:Saliva / Q000032:analysis*; D013997:Time Factors; D014293:Trimethadione / Q000032:analysis / Q000097:blood / Q000378:metabolism*
D010080:Oxazoles; D014293:Trimethadione