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tolbutamide (Orinase)
Tradename: Orinase.
Indications:
- management of non-insulin dependent diabetes mellitus (especially useful in patients with renal insufficiency)
- islet cell tumor
Dosage: 250-3000 mg/day PO divided QD-TID
Tabs: 500 mg. Pharmocokinetics:
1) peak hypoglycemic action: 1-3 hours after PO dose
2) metabolized in the liver by cyt P450 2C9
3) duration of action: 12 hours
Adverse effects:
1) common (> 10%)
- headache, constipation, diarrhea, heartburn, anorexia, epigastric fullness, dizziness
2) less common (1-10%)
- rash, hives, photosensitivity
3) uncommon (< 1%)
- aplastic anemia, hemolytic anemia, bone marrow suppression, cholestatic jaundice, thrombocytopenia, agranulocytosis, hypoglycemia, venospasm, thrombophlebitis, disulfiram- like reaction, leukopenia, tinnitus, SIADH, hypersensitivity
Drug interactions:
1) agents which increase risk of hypoglycemia
a) alcohol
b) beta adrenergic antagonists
c) non-steroidal anti-inflammatory drugs (NSAIDs)
d) sulfonamides
e) clofibrate
f) probenecid
g) dicumarol
h) chloramphenicol
i) MAO inhibitors
2) any drug which inhibits cyt P450 2C9 can increase tolbutamide levels
3) any drug which induces cyt P450 2C9 can diminish tolbutamide levels
Laboratory:
1) specimen: serum
2) methods: HPLC, GLC, color
3) interferences:
a) color: secondary amines, hemolysis
b) GLC: plasma lipids
4) labs with Loincs
- tolbutamide in specimen
- tolbutamide in serum/plasma
- tolbutamide in urine
Mechanism of action:
- 1st generation sulfonylurea.
Interactions
drug interactions
drug adverse effects (more general classes)
monitor with sulfonylureas
Related
cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
General
sulfonylurea
Properties
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 4-6 HOURS
therapeutic-range 80-240 UG/ML
toxic-range >640 UG/ML
protein-binding 90-95%
elimination by hemodialysis -
pregnancy-category C [
D ][
safety in lactation -]
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed,
WB Saunders, Philadelpha 1995
- Prescriber's Letter 13(3): 2006
Cytochrome P450 drug interactions
Detail-Document#: 220233
(subscription needed) http://www.prescribersletter.com
- Deprecated Reference