Trimethoprim elimination

Dofetilide See below3 patients must be hospitalized for 3 days during initiation of therapy Cimetidine, hy d roch I o roth iaz i de, ketoconazole, medroxyprogesterone, promethazine, trimethoprim, verapamil (all inhibit dofetilide elimination)... 

Procainamide 12-1 7 mg/kg, no faster than 20 mg/minute 1-4 mg/minute Cimetidine, ranitidine, and trimethoprim inhibit procainamide elimination... 

Coagulation/flocculation/precipitation of HWWs by means of FeCl3 or Al2(S04)3 seems to be a suitable option for removing lipophilic compounds, such as diclofenac, although it is unable to eliminate many other common hydrophilic PhCs, including carbamazepine, iopromide, diazepam and antibiotics (i.e. roxy-thromycin, erythromycin, trimethoprim), from the liquid phase [66]. 

Intermediate-acting sulfonamides include sulfadiazine and sulfamethoxazole. Sulfamethoxazole is combined with trimethoprim in co-trimoxazole. Sulfadiazine shows good penetration into the cerebrospinal fluid and is effective for cerebral Toxoplasmosis. It has an elimination half-life 10-17 hours which prolonged in renal impairment. 

Only 10-20% is metabolized in the liver and trimethoprim is mainly excreted in urine as unchanged drug with a elimination half-life of 8-11 hours. 

Zidovudine should be used cautiously with any other agent that causes bone marrow suppression, such as interferon-a, trimethoprim-sulfamethoxazole, dap-sone, foscarnet, flucytosine, ganciclovir, and valganci-clovir. Probenecid and interferon-p inhibit the elimination of zidovudine therefore, a dosage reduction of zidovudine is necessary when the drugs are administered concurrently. Ribavirin inhibits the phosphorylation reactions that activate zidovudine, and zidovudine similarly inhibits the activation of stavudine thus, the coadministration of zidovudine with ribavirin or stavudine is contraindicated. 

Lamivudine is associated with an increased risk of pancreatitis in children and should be used with great caution in children who have had pancreatitis or are at high risk for it. Dosage adjustment is necessary in patients with renal impairment. Lamivudine should not be used in combination with zalcitabine, because they inhibit each other s activation by phosphorylation. Trimethoprim inhibits the renal elimination of lamivudine. 

As indicated earher, sulfonamides are effective in both gram-positive and gramnegative bacteria. Mostly prescribed for humans in the United States, in this class is sulfamethoxazole, mostly in combination with trimethoprim (SMZ-TMP) in a 5 1 ratio. Trimethoprim inhibits dihydropholic acid reductase and this, just like sulfonamides, also interferes with the synthesis of folic acid (Fig. 1.8). As a matter of fact, use of the combined SMZ-TMP has been steadily increasing recently as is displayed by the number of prescriptions (Fig. 1.7). Oral doses of sulfonamides are absorbed well and eliminated by the liver and kidney with 20-60% excreted as the parent compound (Queener and Gutierrez, 2003). 

Sulfadiazine is a relatively short-acting sulfonamide with an elimination half-life of about 3 h in cattle. The importance of this drug for control of furunculoses in fish is determined by its combined use with the potentiator trimethoprim. 

When a single dose of radiolabeled sulfadiazine was administered to eels at 7 C (200), highest initial radioactivity was observed in blood, liver, kidney, and skin, with a tendency for accumulation in bile and skin. In another pharmacokinetic study (201) on sea-water rainbow trout fed a combination of sulfadia-zine-trimetlroprim, the elimination process for both sulfadiazine and trimethoprim rapidly reached a point at which only a small but persistent residue was left at 8 C as opposed to 10 C, sulfadiazine was the more potent residue promoter, still being detected at 90 days posttreatment. This was suggested to be a result of the greater binding ability of sulfadiazine as a weak electrolyte. The authors proposed a witlidrawal period for sulfadiazine-trimethoprim of 60 days at water temperatures above 10 C for tabled-size fish, and a prohibition on its use below 10 C for such fish. 

When sulfadiazine in addition with trimethoprim was fed to pigs, the absorption of trimethoprim from the gastrointestinal tract was faster than the absorption of sulfadiazine, whereas the elimination of trimethoprim was slower than... 

Baquiloprim has a high oral bioavailability in animals where it is widely distributed in the body and slowly eliminated (222,223). In cattle, baquiloprim was reported to have a much longer half-life and a larger volume of distribution than trimethoprim (223). Both urine and bile are important routes of elimination. 

In another experiment with rainbow trout given oral trimethoprim at different dosage levels, the elimination half-life in plasma was found to be approxi-... 

In the Accusphere test a freeze-dried sphere containing the test organism Streptococcus thermophilus and bromocresol purple as indicator disperses into the test milk sample. The acidification test is very similar the milk sample is heated to be further inoculated with a Streptococcus thermophilus culture containing yeast extract, bromocresol purple indicator, and trimethoprim. It is then incubated for 2.5 h at 45 C (33). In the presence of inhibitory substances, the organism growth is suppressed, acid production is reduced or eliminated, and the color of the indicator remains unchanged. Addition of penicillinase to a positive milk sample results in change of the color of the indicator from purple to yellow when only -lactams are present. 

PROCAINAMIDE ANTIBIOTICS - TRIMETHOPRIM Procainamide levels are t by trimethoprim Trimethoprim is a potent inhibitor of organic cation transport in the kidney, and elimination of procainamide is impaired Watch for signs of procainamide toxicity 1 the dose of procainamide, particularly in the elderly... 

METHOTREXATE SULFAMETHOXAZOLE/ TRIMETHOPRIM t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Sulfamethoxazole displaces methotrexate from plasma protein-binding sites and also 1 renal elimination of methotrexate. Trimethoprim inhibits dihydrofolate reductase, which leads to additive toxic effects of methotrexate Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasias and liver, renal and pulmonary toxicity... 

In humans, serum creatinine is dependent on non renal factors independent of kidney function e.g. muscle mass, nutritional status, infection, volume of distribution. Also, serum creatinine is dependent on renal factors that are independent of function. For example, certain drugs like trimethoprim and cimetidine elevations in serum creatinine by altering the normal elimination pathways of creatinine. In addition, in humans, alterations in serum creatinine may lag several days behind actual changes in GFR. Earher detection of AKI with a kidney specific biomarker may be essential for early and successful treatment of AKI in humans. 

Trimethoprim is metabolized in the liver to oxide and hydroxyl metabolites. It is eliminated by glomerular filtration and active tubular secretion in the kidneys. In horses, a large percentage of trimethoprim is metabolized before excretion in urine (46%) and feces (52%). The clearance of trimethoprim is affected by urine pH, plasma concentrations and the degree of hydration. In horses, the half-life of trimethoprim is 2-3 h and for pyrimethamine it is 12 h. 

Shoaf S E. Schwark W S, Guard C L 1989 Pharmacokinetics of sulfadiazine/trimethoprim in neonatal male calves effect of age and penetration into cerebrospinal fluid. American Journal of Veterinary Research 50 396-402 Taylor W M, Simpson C F, Martin F G 1972 Certain aspects of toxicity of an amicarbalide formulation to ponies. American Journal of Veterinary Research 33 533-541 Watkins W M, Mosobo M 1993 Treatment of Plasmodium falciparium malaria with pyrimethamine and sulphadoxine a selective pressure for resistance is a function of long elimination half-life. Transactions of the Royal Society of Tropical Medicine and Hygiene 87 75-79... 

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