Tolbutamide dosing

Insulin dose Initial tolbutamide dose Insulin withdrawal... 

Recently a 125 mg tolbutamide dose has been validated, with proposal of the use of just one blood sample collected 24 hour post-dosing. Its safer use needs the drug to be assayed using LC-MS/MS methodology (letter 2004). 

Relative potency alone does not determine dmg selection because maximal effectiveness is similar for all agents. A single daily dose of any sulfonylurea, except tolbutamide, is sometimes adequate to control blood glucose in NIDDM patients. 

Antiadrenergic] Uses HTN Action Centrally acting antihypCTtensive Dose Adults. 250-500 mg PO bid-tid (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 doses (max 40 mg/kg/24 h q6-12h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20 0 mg/kg/24 h X in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine initial transient sedation/drowsiness frequent, edema, hemolytic anemia, hepatic disorders Interactions T Effects W/ anesthetics, diuretics, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide effects W/amphetamines, Fe, phenothiazine, TCAs ... 

Tolbutamide is well absorbed but rapidly metabolized in the liver. Its duration of effect is relatively short, with an elimination half-life of 4-5 hours, and it is best administered in divided doses. Because of its short half-life, it is the safest sulfonylurea for elderly diabetics. Prolonged hypoglycemia has been reported rarely, mostly in patients receiving certain drugs (eg, dicumarol, phenylbutazone, some sulfonamides) that inhibit the metabolism of tolbutamide. 

Hypoglycemia, often during the first hours of combining the two drugs, is the result of an important interaction between sulfonylureas and sulfonamides (184—187). For example, the half-life of tolbutamide was increased from 9.5 to 29 hours by chronic sulfaphenazole and from 9.2 to 26 hours by a single dose of sulfaphenazole (188). Interference by sulfonamides with the protein binding of sulfonylureas may contribute. 

Pond et al (23) reported that the rate of metabolism of tolbutamide was decreased by chronic adminstration of certain drugs, they claimed that the tolbutamide half-life was increased by chronic adminstration of sulphaphenazole (9.5 hrs to 28.6 hrs), phenylbutazone (7.9 hrs to 23.1 hrs), and oxyphenbutazone (8.1 hrs to 30.2 hrs). The rate of elimination of tolbutamide was decreased within one to two hours after a single dose of sulphaphenazole and the half-life was increased from 9.2 hrs to 25.7 hrs. In contrast, phenylbutazone and oxyphenbutazone, adminstered as a single dose 800 mg have no immediate effect on tolbutamide elimination. It is suggested that phenylbutazone and oxyphenbutazone act by inducing a form of a cytochrome P-450 with low activity for tolbutamide hydroxylation, whereare, sulphaphenazole acts by direct inhibition of the microsomol mixed function oxidase system. 

Phenotyping The method measures tolbutamide, its CYP2C9-formed 4 -hydroxylated metabolite and the subsequent carboxytolbutamide metabolite of hydrox-ytolbutamide, formed by dehydrogenase enzymes. The urinary excretion of these two metabolites represented more than 85% dose of administered tolbutamide (Veronese 1990,1993). 

Subjects receive a single oral 500 mg tolbutamide tablet in usual Phase I standard controlled conditions, with care to be paid to blood glucose. Urine is collected from drug intake to 8 or 24 h post-dosing. 

---