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.
Third Department of Internal Medicine, Aichi Medical University, Japan.
A
A
Noda
I
I
Okumura
H
H
Kato
E
E
Ibuki
M
M
Tamada
T
T
Watanabe
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