Methotrexate interaction

Puglisi, G. Fresta, M. Ventura, C. Mazzone, G. Vandelli, M.A. Methotrexate interaction with a lipid membrane model of DPPC. J. Thermal Anal. 1995, 44, 1287-1299. 

Wallace CA, Smith AL, Sherry DD. Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis. J Rheumatol 1993 20(10) 1764-8. 

Dalle JH, Auvrignon A, Vassal G, Leverger G, Possible ciprofloxacin-methotrexate interaction a report of 2 cases, Intersci Conf Antimicrob Agents Cnemother (2000) 40,477. 

Figure 1.5 Interactions of the dihydrofolate reductase active site with the inhibitor methotrexate (left) and the substrate dihydrofolate (right).

We have already used the interactions of methotrexate with dihydrofolate reductase (DHFR) several times within this text to illustrate some key aspects of enzyme inhibition. The reader will recall that methotrexate binds to both the free enzyme and the enzyme-NADPH binary complex but displays much greater affinity for the latter species. The time dependence of methotrexate binding to bacterial DHFR was studied by Williams et al. (1979) under conditions of saturating [NADPH], In the presence of varying concentrations of methotrexate, the progress curves for DHFR activity became progressively more nonlinear (Figure 6.14). The value of kobs from... 

Among its inhibitors are methotrexate (MTX), trimethoprim, and other derivatives of pyrimidines, triazines, pteridines, and related heterocyclic compounds. Some of these inhibitors, such as MTX, bind more tightly to Escherichia coli enzyme than does the substrate dihydrofolate. This fact has been attributed to ion-pair formation between protonated MTX and a negative carboxyl, presumably Asp-27, as well as to hydrophobic interactions.33... 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

Ueda, K., Kato, Y., Komatsu, K., Sugiyama, Y., Inhibition of biliary excretion of methotrexate by probenecid in rats quantitative prediction of interaction from in vitro data, J. Pharmacol. Exp. Ther. 2001,... 

The above model was used to study the binding of methotrexate, and analogues of it, to wild-type and mutant forms of human dihydrofolate reductase (DHFR).29 This turned out to be a particularly difficult test because of the three ionized groups of methotrexate. The overall electrostatic interactions of this inhibitor amount to around -500 kcal/mol and MD trajectories of length more than a ns were required in order to get average... 

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

Vincristine has been shown to enhance the accumulation of the folate antagonist methotrexate in murine leukemia cells, and the enhancement has been shown to involve inhibition of a specific efflux route for methotrexate (25) the suggestion has been made that the effect of vincristine on methotrexate efflux may be related to alterations of cell membrane electrical activity that appear to occur when cells are treated with vincristine. In this connection, it is worth mentioning that association of tubulin with membrane structures from bovine brain has been described 25a). Both vinblastine and vincristine have been reported to enhance the accumulation of the folate antagonist methotrexate in human leukemic cells (S) there is no evidence, however, to indicate that this interaction has significance in a clinical setting. 

Drugs that may interact include chlorpropamide, lithium, methotrexate, salicylates, tetracyclines, anorexiants, flecainide, mecamylamide, quinidine, and sympathomimetics. 

Drugs that may interact with folic acid include aminosalicylic acid, oral contraceptives, dihydrofolate reductase inhibitors (eg, methotrexate, trimethoprim), sulfasalazine, hydantoins. 

Drug/Lab test interactions Methotrexate, pyrimethamine, and most antibiotics invalidate folic acid and vitamin Bi2diagnostic microbiological blood assays. 

Drugs that may affect amiodarone include hydantoins, cholestyramine, fluoroquinolones, rifamycins, ritonavir, and cimetidine. Drugs that may be affected by amiodarone include anticoagulants, beta-blockers, calcium channel blockers, cyclosporine, dextromethorphan, digoxin, disopyramide, fentanyl, flecainide, hydantoins, lidocaine, methotrexate, procainamide, quinidine, and theophylline. Drug/Lab test interactions Amiodarone alters the results of thyroid function tests, causing an increase in serum T4 and serum reverse T3 levels and a decline in... 

Drugs that may interact with sulfasalazine include digoxin, sulfonylureas, folic acid, cyclosporine, methotrexate, thiopurines, and warfarin. 

Drugs that may interact with sulfonamides include oral anticoagulants, cyclosporine, hydantoins, methotrexate, and sulfonylureas. 

Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and Gl toxicity have occurred with coadministration of methotrexate (usually in high dosage) along with some NSAIDs (see Precautions. Drug Interactions). 

Drug/Food interactions Food may delay the absorption and reduce the peak concentration of methotrexate. 

No drug interaction studies have been conducted in humans. Animal studies indicate no change in the clearance or toxicity of either methotrexate or anakinra when the two agents are administered together. Concomitant administration of a TNF blocker appears to increase the risk of serious infection. The response to vaccines may be diminished in patients taking anakinra. 

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