Penicillins Methotrexate

OAT Penicillin Methotrexate Cidofovir Furosemide Various Probenecid NSAIDS Probenecid Probenecid Uremic Toxins f duration of action of penicillin f plasma exposure of methotrexate leading to toxicity J, kidney accumulation and lower incidence of cidofovir nephrotoxicity J, diuretic activity of furosemide J, excretion of OAT substrates... 

Effects Uricosuric drugs act primarily in the kidney and inhibit the secretion of a large number of other weak acids (eg, penicillin, methotrexate) in addition to inhibiting the reabsorption of uric acid. 

The co-administration of drugs which inhibit the transporters involved in renal tubular secretion can reduce the urinaty excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, probenecid increases the plasma concentration and the duration of effect of penicillin by inhibiting its renal tubular secretion. It also elevates the plasma concentration of methotrexate by the same mechanism, provoking its toxic effects. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

Penicillamine (Cuprimine), a derivative of penicillin, is officially classified as a chelating agent that is often used in the treatment of heavy metal intoxication (e.g., lead poisoning). In addition, this drug has been used in patients with severe rheumatoid arthritis, and seems to be as effective as other DMARDs such as methotrexate, sulfasalazine, and gold therapy.68 98 Penicillamine, however, tends to be substantially more toxic than other DMARDs, and is therefore used rarely in the treatment of specific patients with rheumatoid arthritis.68... 

Williams WM, Chen TS, Huang KC. Effect of penicillin on the renal tubular secretion of methotrexate in the monkey. Cancer Res 1984 44 1913-1917. 

Neomycin Neomycin interferes with the absorption of digoxin, methotrexate, vitamins, some penicillins, acarbose, and oral contraceptives. 

Tetracycline Tetracycline injections have an acid pH. Incompatibility may reasonably be expected with alkaline preparations or with drugs unstable at low pH. Care should be taken when administering tetracyclines, since chelation takes place with metal ions. Tetracyclines interact with inorganic metal ions. They should not be used with drugs that cause hepatotoxicity and nephrotoxicity (e.g., digoxin, theophylline, ergot alkaloids, methotrexate, oral contraceptives, and penicillins). 

METHOTREXATE PENICILLINS t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Penicillins 1 renal elimination of methotrexate by renal tubular secretion, which is the main route of elimination of methotrexate. Penicillins compete with methotrexate for renal elimination. Displacement from proteinbinding sites may occur and is only a minor contribution to the interaction Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasia, liver toxicity and pulmonary toxicity. Do FBCs and LFTs prior to concurrent treatment... 

Interference with active transport. Organic acids are passed from the blood into the urine by active transport across the renal tubular epithelium. Penicillin is mostly excreted in this way. Probenecid, an organic acid that competes successfully with penicillin for this transport system, may be used to prolong the action of penicillin when repeated administration is impracticable, e.g. in sexually transmitted diseases, where compliance is notoriously poor. Interference with renal excretion of methotrexate by aspirin, of zidovudine by probenecid and of digoxin by quinidine, contribute to the potentially harmful interactions with these combinations. 

Electrodes based on the immobilization of enzymes at the electrode surface have been reported for a few pharmaceutical applications. Seegopaul and Rechnitz developed a CO2 electrode that responds to methotrexate due to the inhibition of dihydrofolate reductase by the analyte. Additional applications have included the detection of penicillin consumption by penicillinase as well as urea by urease with a pH electrode and analysis of L-ascorbic acid by ascorbate oxidase.f ... 

Concomitant penicillin administration has been reported to exacerbate the hematological toxicity of low-dose methotrexate (143). This could have been due to inhibition of the tubular secretion of methotrexate. 

Clinically important, potentially hazardous interactions with amoxicillin, ampicillin, antacids, bacampicillin, calcium carbonate, carbenicillin, cloxacillin, digoxin, methotrexate, methoxyflurane, mezlocillin, nafcillin, oxacillin, penicillins, piperacillin, ticarcillin, zinc... 

Clinically important, potentially hazardous interactions with amphotericin B, benzodiazepines, doripenem, ertapenem, fludoxacillin, furosemide, glibenclamide, ketoprofen, ketorolac, methotrexate, NSAIDs, pemetrexed, penicillamine, penicillin G, penicillin V, salicylates, sulfamethoxazole, sulfonamides, torasemide, torsemide... 

Clinically important, potentially hazardous interactions with acitretin, aluminum hydroxide, amoxicillin, ampicillin, antacids, bacampicillin, betamethasone, bismuth, bromelain, calcium, carbenicillin, cholestyramine, doxacillin, corticosteroids, dairy products, dicloxacillin, didanosine, digoxin, food, glidazide, iron, isotretinoin, methicillin, methotrexate, methoxyflurane, mezlocillin, nafcillin, oxacillin, penicillins, piperacillin, retinoids, rocuronium, strontium ranelate, sucralfate, ticarcillin, vitamin A, zinc... 

Transporter absorptive effects predominant Examples. Acyclovir, Amiloride -, Amoxicillin Atenolol Atropine, Bidisomide Bisphosphonates Captoprit, Cefazolin Cetirizine Cimetidine Ciprofloxacin, Cloxacillin Dicloxacillin Erythromycin - -, Famotidine Fexofenadine Folinic acid Furosemide, Ganciclovir Hydrochlorothiazide, Lisinopril Metformin Methotrexate, Nadolol Penicillins Pravastatin Ranitidine Tetracycline Trimethoprim Valsartan Zalcitabine... 

Noninterfering acetaminophen, acyclovir, allopurinol, amoxicillin, amphotericin B, am-picillin, aspirin, azlocillin, bendrofluazide, bumetanide, buprenorphine, carbenidllin, cefazolin, cefotaxime, cefoxitin, ceftazidime, cefuroxime, cephalexin, chlorambucil, chloramphenicol, chlordiazepoxide, chlorpheniramine, chlorpropamide, cyclophosphamide, cyclosporin, C5d arabine, daunorubicin, dextropropoxyphene, dihydrocodeine, domperidone, flucytosine, furosemide, gentamicin, griseofulvin, melphalan, methotrexate, metochlo-pramide, metronidazole, miconazole, nabilone, netilmicin, nicotinamide, nitrazepam, penicillin G, piperacillin, prednisolone, procarbeizine, prochlorperazine, riboflavin, rifampin, sulfamethoxazole, thioguanine, tobramycin, tolbutamide, trimethoprim... 

The above compounds are the glamorous pharmaceuticals, the results of fairly recent research and mostly based on a clear idea of the enzyme systems they are supposed to influence. The most widely consumed pharmaceuticals, however, are aspirin, paracetamol (called acetaminophen in the USA) and vitamin C. These can all be bought over-the-counter. Annual world consumption is of the order of 50 000 tonnes each, an order of magnitude higher than consumption of, say, penicillin V. At the other extreme come materials such as the anti-cancer drag, methotrexate, with annual... 

Severe drug-drug interactions are known to occur between methotrexate and NSAIDs, probenecid, and penicillin G partially due to inhibition of renal... 

OAT-mediated secretion of methotrexate. By using mouse proximal tubule cells stably expressing human transporters, methotrexate has been demonstrated to be taken up via hOAT3 and hOATl at the basolateral side of the proximal tubule and effluxed or taken up at the apical side via hOAT4, where drug interactions occur between methotrexate and NSAIDs, probenecid, and penicillin G (Takeda et al., 2002). 

Cephalosporins Dapsone Methotrexate Penicillins Quinolones Probenecid Serum levels of drug affected raised possibility of toxicity with some drugs... 

---