Trimethoprim renal clearance

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. 

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... 

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... 

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. 

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. 

Trimethoprim decreases the renal clearance of both procainamide and its active metabolite by competing for active tubular secretion. It may also cause a small increase in the conversion of procainamide to A-acetylpro-cainamide. ... 

ML. Trimethoprim inhibition of the renal clearance of procainamide N-acetylprocaina-... 

In a study, 6 HIV-positive subjects were given co-trimoxazole 960 mg daily with a single 3-mg/kg dose of cidofovir with probenecid given on day 7. The AUC and maximum plasma concentrations of both trimethoprim and sulfamethoxazole were decreased by about 30% and renal clearance was significantly increased. The pharmacokinetics of cidofovir were not affected. ... 

In a study of 14 HIV-positive patients taking co-trimoxazole 960 mg daily for 5 days, it was found that the AUC of a single 300-mg dose of lamivudine given on day 4 was increased by 43% and the renal clearance was decreased by 35%. The pharmacokinetics of the trimethoprim and the sulfamethoxazole were unaffected. Similarly, in a population pharmacokinetic analysis, the concurrent use of lamivudine and co-trimoxazole was associated with a 31% reduction in the apparent oral clearance of lamivudine, and an estimated 43% increase in steady-state lamivudine levels. The UK manufacturer notes that the interaction is due to trimethoprim, and that sulfamethoxazole did not interact. ... 

Trimethoprim 200 mg twice daily for 10 days did not affect the total body clearance of a single 1-mg intravenous dose of digoxin in 6 young healthy subjects (aged 24 to 31). Renal clearance was reduced, but this was compensated for by an increase in extra-renal clearance. ... 

It is suggested that trimethoprim reduces the renal excretion of digoxin. The paradoxical finding between the elderly patients and the young healthy subjects may be the age difference, probably as the elderly patients may not be able to accommodate an increase in extra-renal digoxin clearance. 

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