The excretion of 5,5-dimethyl-2,4-oxazolidinedione from the canine pancreas and liver

Noda, Aiji; Toda, Y; Hayakawa, Tetsuo; Nakajima, Sumio

doi:10.1007/bf01076601

Cited by 13 publications

(3 citation statements)

References 10 publications

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“…A close correspondence between observed and theoretical concentration-time curves of plasma DMO suggests that TMO is a medica tion with a simple metabolic process in the body, including intestinal absorption, com plete déméthylation to DMO, probably in the liver, and excretion of DMO to pancreatic juice, bile [3,18], and urine [19,20]. The extremely low TMO concentration in plasma during the repeated oral administration of the drug can be interpreted by the fact that the biological half-life of the drug is short (5.4 ± 0.4 h; mean ± SEM) as a result of the rapid conversion of the drug to DMO [14].…”

Section: Repeated Oral Administration Oftmo and Concentration-time Cumentioning

confidence: 61%

“…Pancreatic DMO clearance (DMO output/DMO concentration in plasma) increased, de pending on the flow rate, the bicarbonate concentration, and pH of pancreatic juice. Pan creatic excretion of TMO was zero or extremely low.There are various studies reporting that dimethadione (5,5 -dimethyl -2,4 -oxazolidinedione; DMO), a weak organic acid with a molecular weight of 129.1, a pKA of 6.13 at 37 0 C [ 1,2], and an oil-water partition ratio of more than 5 [2], is excreted into pancreatic juice in anesthetized dogs [3,4] and in human subjects [5][6][7][8][9], DMO is the demethylated product of trimethadione (3,5,5-trimethyl-2,4-oxazolidinedione; TMO) which is a more or less obsolete antiepileptic agent, mainly used to prevent absence seizures. The pre vious studies concerning pancreatic excretion of DMO were performed with a single or a continuous intravenous injection of DMO per se in dogs, and with the oral administration of a given dose of TMO (about 1.3 g daily) to human subjects over a period of 3 days.…”

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confidence: 99%

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Pancreatic Excretion of Dimethadione and Trimethadione by Repeated Oral Administration of Trimethadione in Dogs

Noda¹,

Okumura²,

Kato³

et al. 1990

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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.

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Section: Repeated Oral Administration Oftmo and Concentration-time Cumentioning

confidence: 61%

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confidence: 99%

Pancreatic Excretion of Dimethadione and Trimethadione by Repeated Oral Administration of Trimethadione in Dogs

Noda¹,

Okumura²,

Kato³

et al. 1990

Digestion

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“…Dimethadione accumulates significantly in the pancreas [8], is excreted into the pancreatic juice at high concentrations [9][10][11][12], and dissolves CaCO 3 [13][14][15][16]. Oral litholysis using a dimethadione precursor, trimethadione, was previously developed and shown to have efficacy for CCP as a noninvasive oral litholytic therapy (OLT) [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Oral Litholysis in Patients with Chronic Calcific Pancreatitis Unresponsive to or Ineligible for Extracorporeal Shock Wave Lithotripsy and Endoscopic Therapy

Hamano

Noda²,

Ibuki³

et al. 2019

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Background/Aims: Our study aimed to evaluate the effect of oral litholysis in patients with chronic calcific pancreatitis (CCP) unresponsive to or ineligible for extracorporeal shock wave lithotripsy (ESWL) and endoscopic therapy. Methods: Trimethadione, an antiepileptic agent, was administered orally at a dose of 0.6–0.9 g/day to 15 patients with this condition. Treatment outcome was evaluated by assessment of dissolution of the pancreatic stones on plain X-ray films and computed tomography scans of the upper abdomen. Plasma glucose, hemoglobin A1c, and body mass index (BMI) were also monitored throughout the therapy. Results: Litholysis was observed in 13 out of 15 patients (86.7%) and was definite in 10 and partial in 3. Six patients had pancreatitis attacks during the therapy; 5 of whom showed definite litholysis and had only 1 mild attack. Of the 11 patients with normal or impaired glucose tolerance at baseline, none developed diabetes mellitus and all showed litholysis. BMI significantly increased in patients whose pancreatic stones dissolved. There was no vital organ impairment by trimethadione. Conclusion: Oral litholysis using trimethadione may represent a noninvasive and effective complementary treatment in patients with CCP unresponsive to or ineligible for ESWL and endoscopic therapy.

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Pancreatolithiasis and Pancreatic Carcinoma

Noda¹

1977

Arch Intern Med

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The excretion of 5,5-dimethyl-2,4-oxazolidinedione from the canine pancreas and liver

Cited by 13 publications

References 10 publications

Pancreatic Excretion of Dimethadione and Trimethadione by Repeated Oral Administration of Trimethadione in Dogs

Pancreatic Excretion of Dimethadione and Trimethadione by Repeated Oral Administration of Trimethadione in Dogs

Oral Litholysis in Patients with Chronic Calcific Pancreatitis Unresponsive to or Ineligible for Extracorporeal Shock Wave Lithotripsy and Endoscopic Therapy

Pancreatolithiasis and Pancreatic Carcinoma

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