Pancreatic excretion of dimethadione and trimethadione by repeated oral administration of trimethadione in dogs.
To examine pancreatic excretion of dimethadione (DMO), a weak organic acid, as well as of its precursor trimethadione (TMO), TMO was given orally to dogs with pancreatic fistulae at a dose of 10-160 mg/kg/day over a period of 14 days. Blood samples were taken once a day during the administration of TMO and for 7 days after discontinuation of the drug. On the 15th day, pancreatic juice was collected under stimulation by secretin (2 Crick-Haper-Raper units/kg/h). DMO concentration in plasma reached a maximal plateau around the 10th day after starting TMO administration, and depended directly on the dose of TMO. Pancreatic excretion of DMO at a steady state closely depended on both the dose of TMO and the DMO concentration in plasma. The pancreatic juice/plasma concentration ratio for DMO exceeded 1.0 at a steady rate and decreased with the increased flow rate. Pancreatic DMO clearance (DMO output/DMO concentration in plasma) increased, depending on the flow rate, the bicarbonate concentration, and pH of pancreatic juice. Pancreatic excretion of TMO was zero or extremely low.
Noda
A
A
Third Department of Internal Medicine, Aichi Medical University, Japan.
Okumura
I
I
Kato
H
H
Ibuki
E
E
Tamada
M
M
Watanabe
T
T
D000284:Administration, Oral; D000818:Animals; D004114:Dimethadione / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010179:Pancreas / Q000378:metabolism*; D010185:Pancreatic Fistula / Q000378:metabolism; D010189:Pancreatic Juice / Q000378:metabolism; D014293:Trimethadione / Q000008:administration & dosage / Q000378:metabolism*
D004114:Dimethadione; D014293:Trimethadione