Trimethoprim clearance

Methotrexate clearance can be decreased by the coadministration of NSAIDs however, this not usually a problem with the low doses of methotrexate used to treat arthritis. Methotrexate can be displaced from plasma protein binding sites by phenylbutazone, pheny-toin, sulfonylureas, and sulfonamides and certain other antibiotics. The antifolate effects of methotrexate are additive with those of other folate-inhibitory drugs, such as trimethoprim. 

Several drug interactions involving amantadine and rimantadine are clinically significant. Anticholinergic drugs can potentiate the toxicity of amantadine. Thiazide-triamterene, trimethoprim-sulfamethoxazole, quinine, and quinidine increase plasma amantadine levels. Cimetidine decreases rimantadine clearance, and aspirin and acetaminophen decrease rimantadine plasma levels. 

The most common adverse effects of lamivudine seen at doses used to treat HBV are mild they include headache, malaise, fatigue, fever, insomnia, diarrhea, and upper respiratory infections. Elevated alanine aminotransferase (ALT), serum lipase, and creatine kinase may also occur. The safety and efficacy of lamivudine in patients with decompensated liver disease have not been established. Dosage adjustment is required in individuals with renal impairment. Coadministration of trimethoprim-sulfamethoxazole decreases the renal clearance of lamivudine. 

Therefore, when 1 part of trimethoprim is given with 5 parts of sulfamethoxazole (the ratio in the formulation), the peak plasma concentrations are in the ratio of 1 20, which is optimal for the combined effects of these drugs in vitro. About 30-50% of the sulfonamide and 50-60% of the trimethoprim (or their respective metabolites) are excreted in the urine within 24 hours. The dose should be reduced by half for patients with creatinine clearances of 15-30 mL/min. 

Trimethoprim- sulfamethoxazole Synergistic combination of folate antagonists blocks purine production and nucleic acid synthesis Bactericidal activity against susceptible bacteria Urinary tract infections Pneumocystis jiroveci pneumonia toxoplasmosis nocardiosis Oral, IV renal clearance (half-life 8 h) dosed every 8-12 h t formulated in a 5 1 ratio of sulfamethoxazole to trimethoprim Toxicity Rash, fever, bone marrow suppression, hyperkalemia... 

On the other hand, the volume of disfiibution is significantly increased for orally administered trimethoprim in feverish rabbits compared with their healthy counterparts and absorption is reduced (38). The significance of these changes can be appreciated if one considers that the total body clearance of a drug is... 

DIGOXIN TRIMETHOPRIM, CO-TRIMOXAZOLE Trimethoprim may t plasma concentrations of digoxin, particularly in elderly people Uncertain postulated that trimethoprim 1 renal clearance of digoxin Monitor digoxin levels watch for digoxin toxicity... 

The use of fixed combination of a thiazide and a potassium-sparing drug, often Moduretic (hydrochlorothiazide 50 mg with amiloride 5 mg), has been consistently implicated in diuretic-induced hyponatremia. Treatment with chlorpropamide (200-800 mg/day) along with Moduretic has precipitated hyponatremia in several cases (96). Simultaneous use of Moduretic with trimethoprim has also been reported to increase the risk (97). The mechanism appears to be impairment of the clearance of free water, resulting in dilutional hyponatremia. Whether... 

The interaction of rifampicin with trimethoprim has been reviewed (105). Rifampicin has a small effect on the clearance of trimethoprim bnt it is not clinically significant... 

In one pharmacokinetic study in eight HIV-infected subjects, the renal clearance of zidovudine was significantly reduced by trimethoprim (201). The authors concluded that zidovudine dosages may need to be reduced if trimethoprim is given to patients with impairment of liver function or glucuronidation. Zidovudine, on the other hand, did not alter the pharmacokinetics of trimethoprim. 

Naderer O, Nafziger AN, Bertino JS Jr.. Effects of moderate-dose versus high-dose trimethoprim on serum crea-tiniue aud creatiuiue clearance and adverse reactions. Antimicrob Agents Chemother 1997 41(ll) 2466-70. 

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. 

The effect of experimentally induced bacterial infections, all of which have in common the presence of fever, on the disposition of various antimicrobial agents in pigs is presented in Table 3.1. In the infected pigs, the apparent volume of distribution of penicillin G, ampicillin and, to a lesser extent, trimethoprim is increased, of enrofloxacin and sulphonamides remains unchanged, and of oxytetracycline is decreased. The systemic clearance of penicillin G, ampicillin and trimethoprim is increased, of sulphamethoxazole and sulphadimethoxine remains unchanged, and of sulphadimidine,... 

Several other agents have been used to prevent recurrence of ANCA-associated diseases. Mycophenolate mofetU has been used anecdotally with favorable results for remission maintenance. Methotrexate has also been used however, it should not be given when the creatinine clearance is <50 mL/min. Trimethoprim-sulfamethoxazole was found to reduce ANCA-associated vasculitis, especially in the upper respiratory tract. 

Kastmp J, Petersen P, Bartram R, Hansen JM. The effect of trimethoprim on serum creatinine. Brit J Urol 1985 57 265-268. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976 16 31-41. 

Nakatani-Freshwater, T., Babayeva, M., Dontabhaktuni, A., Taft, D. R. (2006). Effects of trimethoprim on the clearance of apricita-bine, a deoxycytidine analog reverse transcriptase inhibitor, and Lamivudine in the isolated perfused rat kidney. The Journal of Pharmacology and Experimental Therapeutics, 319, 941—947. 

Following oral administration, lamivudine is absorbed rapidly with a bioavailability of about 80% in adults. Peak plasma levels average approximately 1000 ng/mL after 100-mg doses. Lamivudine is distributed widely in a volume comparable with total-body water. The plasma t,/2 of elimination averages about 9 hours, and approximately 70% of the dose is excreted unchanged in the urine. About 1% is metabolized to an inactive trawY-sulfoxide metabolite. In HBV-infected children, doses of 3 mg/kg per day provide plasma exposure and trough plasma levels comparable with those in adults receiving 100 mg daily. Dose reductions are indicated for moderate renal insufficiency (creatinine clearance <50 ml/min). Trimethoprim decreases the renal clearance of lamivudine. 

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