Tolbutamide interactions

Tolbutamide is metabolized by hydroxylation of the methyl tolyl group in man (80), forming hydroxy tolbutamide. Hydroxytolbutamide is further metabolized to carboxytolbutamide (80,81). However, it is the initial hydroxylation that is rate limiting for elimination, accounting for approximately 85% of the clearance in man. This elimination pattern has enabled urinary ratios to be used to assess tolbutamide interactions, which gave a good correlation with total clearance on coadministration with sulfaphenazole (82). 

Andreasen PB, Simonsen K, Brocks K, Dimo B, Bouchelouche P. Hypoglycaemia induced by azapropazone tolbutamide interaction. Br J Clin Pharmacol 1981 12(4) 581-3. 

Some lists, reviews and books on interactions say that chloramphenicol, aminosalieylie aeid, sodium salieylate, sulfamethoxypyridazine, tetracycline or tolbutamide interact with methotrexate, apparently based largely on the preliminary findings of a study in which male mice were treated for 5 days with each of 4 doses of methotrexate (1.53 to 12.25 mg/kg intravenously) and immediately afterwards with non-toxic intraperitoneal doses of the drugs listed. These drugs were said to decrease the lethal dose and/or decrease the survival time of the mice That is to say, the toxicity of the methotrexate was increased. The reasons are not understood, but it is suggested that displacement of the methotrexate from its plasma protein binding sites could result in a rise in the levels of unbound and active methotrexate, and in the case of sodium salicylate to a decrease in renal clearance. 

Tolbutamide Tolbutamide, l-butyl-3-p-toluenesulfonylurea (26.2.2), is made in a single step reaction by interaction of p-toluenesulfonylamide (in the form of sodium salt) with butyUso-cyanate [17-20]. 

Drug/Lab test interactions A metabolite of tolbutamide in the urine may give a false-positive reaction for albumin if measured by the acidification-after-boiling test. 

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 ... 

Ishihara K, Kashida H, Yuzurihara M, et al. Interaction of drugs and Chinese herbs pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica. J Pharm Pharmacol 2000 52 1023-1029. 

Drug Interactions Increased prothrombin time after warfarin administration Phenytoin Cyclosporine Tolbutamide Tacrolimus Glyburide Glipizide Rifampin Cisapride Terfenadine Astemizole Theophylline ... 

The interaction of tolbutamide with diltiazem has been studied in eight healthy men (169). Tolbutamide had no effect on diltiazem, but diltiazem increased the AUC of tolbutamide by 10% without an effect on blood glucose... 

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. 

Most reports of this interaction have described hypoglycemia with tolbutamide in combination with sulfaphenazole (184,185,188,189), sulfafurazole (185), or co-trimoxazole (187,190). The inhibitory effect of sulfonamides on tolbutamide metabolism is mediated by CYP2C9 (191). 

Dixit AA, Rao YM. Pharmacokinetic interaction between diltiazem and tolbutamide. Drug Metabol Drug Interact 1999 15(4) 269-77. 

Komatsu K, Ito K, Nakajima Y, Kanamitsu S, Imaoka S, Funae Y, Green CE, Tyson CA, Shimada N, Sugiyama Y. Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments. Drug Metab Dispos 2000 28(4) 475-81. 

Nirmala and Gowda (2) have reported that tolbutamide crystallizes in the orthorhombic space group Pn2 a, with a=20.16 (2), b=9.05 (1), C=7.85 (1) A0, Z=4, Dc=1.25, Dm=1.24 Mgm 3 and U (CuKa)=1.968 mm l. The structure was solved by the Patterson search method and refined to an R factor of 0.083 for 615 visually measured reflections. The structure is stabilized by hydrogen bonding between the polar group and Van der waals interactions between the non polar groups. The... 

Krishnaiah YSR, Satyanarayana S, Visweswaram D. Interaction between tolbutamide and ketoconazole hi healthy subjects. Br J Clin Pharmacol 1994 37 205-207. 

Incompatibilities of metoclopramide depend on drug concentration, pH, and temperature. It is incompatible with cephalosporins, chloramphenicol, sodium bicarbonate, doxorubicin, cisplatin, and cyclophosphamide. Caution should be exercised with simultaneous administration of metoclopramide with lithium, sym-pathomimetics, antidepressants, bromocriptine, and carbamazepine. Omperazole interacts with tolbutamide, clarithromycin, and phenytoin. Coadministration of rantidine and cisapride increases the plasma concentration of rantidine. Abuse of senna laxative has been reported and may cause hepatitis.176-178... 

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