Cyclophosphamide Chloramphenicol

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

Drugs that may affect chloramphenicol include barbiturates, rifampin, and hydantoins. Drugs that may be affected by chloramphenicol include barbiturates, anticoagulants, cyclophosphamide, hydantoins, iron salts, penicillins, sulfonylureas, and vitamin B- 2-... 

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... 

Mechanism-based inactivation of CYP450 (or suicide inhibition) occurs when a non-toxic drug is metabolised by CYP450 to generate a metabolite that can bind irreversibly with the enzyme. The mechanism of inhibition usually involves free-radical alkylation or acylation of the active site and results in destruction of enzyme activity. Examples of drugs that act in this way include the antibiotic chloramphenicol and the anticancer agent cyclophosphamide. 

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... 

Some limited evidence suggests that chloramphenicol may reduce the production of the active metabolites of cyclophosphamide. Whether this reduces its therapeutic efficacy remains to be determined. 

Cyclophosphamide itself is inaetive, but after administration it is metabolised to aetive alkylating metabolites. A study in animals found that pretreatment with chloramphenieol redueed the effects of cyclophosphamide and redueed the produetion of its aetive metabolites. Although another animal study also found a reduetion in lethality of cyclophosphamide with ehloramphenicol, the immunosuppressive effect of cyclophosphamide was unehanged. A study in 4 patients found that chloramphenicol 1 g twice daily for 12 days prolonged the mean serum half-life of a single intravenous dose of cyclophosphamide from 7.5 to 11.5 hours, but did not signifieantly affect the AUC of the metabolites. ... 

Chloramphenicol is an inhibitor of the cytochrome P450 isoenzyme subfamily CYP2B, which is partially responsible for the activation of cyclophosphamide. It therefore seems possible that a reduction in the activity of cyclophosphamide may occur, but the extent to which this affects treatment with cyclophosphamide is uncertain. Concurrent use need not be avoided, but be alert for evidence of a reduced response. More study is needed. 

Strain. By these criteria, methyl methanesulfonate, A -acetoxyfluorenylacet-amide, captan, and others are preferential inhibitors of the pol Ai strain (Tables 7 and 8). On the other hand, streptomycin and chloramphenicol, although they induce lethality in both indicator strains, do not preferentially kill the pol Ar strain (SI = 1.12 and 1.02, respectively). It should be noted that this procedure is compatible with metabolic activation. Thus, the precarcinogens 2-aminofluorene and cyclophosphamide, which require metabolic activation by hepatic enzymes, do not preferentially inhibit the pol Ai strain in the absence of rat liver microsomes, but do so in the presence of this preparation (Tables 7 and 8). This procedure has the added advantage that results obtained by this modified pol Ai assay are expressed quantitatively, rather than as differences in the diameters of the zones of growth inhibition. As will be seen below, this modified procedure greatly increases the usefulness of the pol A assay (Table 9). 

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