Trimethoprim Subject

In a study in 9 healthy subjects trimethoprim 160 mg twice daily for 3 days increased the AUC and the maximum plasma level of a single 250-microgram dose of repaglinide by 61% and 41%, respectively. However, the blood glucose-lowering effect of repaglinide was unchanged. ... 

In a study in 10 healthy subjects trimethoprim 160 mg twice daily for 4 days increased the AUC of a single 4-mg dose of rosiglitazone given on day 3 by 37%. The half-life of rosiglitazone was increased by 26% but the peak plasma level was only slightly affected (14% inerease). Similarly, in another study, trimethoprim 200 mg twiee daily for 5 days increased the AUC ofa single 8-mg dose of rosiglitazone by 31% and increased the half-life by 27% ... 

Neimi M, Kajosaari LI, Neuvonen M, Backman JT, Neuvonen PJ. The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects. Br J Clin Pharmacol 2004 57 441-7. 

Hruska MW, Amico JA, Langaee TY, Ferrell RE, Fitzgerald SM, Frye RF. The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects. Br J Clin Pharmacol 2005 59 70-9. 

Don BR. The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects. Clin Nephrol 2001 55 45-52. 

After a single oral dose containing 800 mg of sulphamethoxazole and 160 mg of trimethoprim given to 8 subjects, peak serum concentrations of 28 to 45 pg/ml (mean 39) of sulphamethoxazole were attained in 2 to 4 hours. Peak concentrations of trimethoprim of 0.9 to 1.5pg/ml (mean... 

Oral dosing of 5 subjects with 800 mg of sulphamethoxazole and 160 mg of trimethoprim twice daily, produced minimum steady-state plasma concentrations of about 55 pg/ml of sulphamethoxazole and 1.7 pg/ml of trimethoprim, on the ninth day (P. Kremers et al., J. clin. Pharmac., 1974, /4,112-117). 

Following oral administration of 400 mg twice a day to 10 subjects (in combination with trimethoprim 80 mg), a mean maximum steady-state plasma concentration of 75 pg/ml and a mean trough concentration of 42 pg/ml were reported (I. D. Watson et al., Br. J. din. Pharmac., 1982, 14, 437-443). 

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. 

Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an essential enzyme required for normal folate metabolism in prokaryotes and eukaryotes. Its role is to maintain necessary levels of tetrahydrofolate to support the biosynthesis of purines, pyrimidines and amino acids. Many compounds of pharmacological value, notably methotrexate and trimethoprim, vork by inhibition of DHFR. Their clinical importance justified the study of DHFR in the rapidly evolving field of enzymology. Today, there is a vast amount of published literature (ca. 1000 original research articles) on the broad subject of dihydrofolate reductase contributed by scientists from diverse disciplines. We have selected kinetic, structural, and computational studies that have advanced our understanding of the DHFR catalytic mechanism with special emphasis on the role of the enzyme-substrate complexes and protein motion in the catalytic efficiency achieved by this enzyme. 

As part of a larger study, 6 HIV-positive subjects received atovaquone 500 mg once daily, co-trimoxazole 960 mg (trimethoprim/sulfamethoxa-zole 160/800 mg) twice daily, or the combination, taken with food. There was no change in steady-state atovaquone levels but there was a minor 17% decrease in steady-state trimethoprim levels and a minor 8% decrease in sulfamethoxazole levels when both drugs were given together. ... 

Eight healthy subjects were given procainamide 500 mg every 6 hours for 3 days. The concurrent use of trimethoprim 200 mg daily increased the AUCo i2 of procainamide and its aeti ve metabolite, AZ-aeetylprocainamide (NAPA), by 63% and 51%, respeetively. The renal elearance of procainamide and NAPA decreased by 47% and 13%, respeetively. The QTc prolonging effects of procainamide were inereased to a significant, but slight, extent by trimethoprim. Another study found that trimethoprim 200 mg... 

A study in 12 healthy subjects given co-trimoxazole (trimethoprim and sulfamethoxazole) 9 mg daily for 7 days found that a single 1.2-g dose of azithromycin given on day 7 did not alter the pharmacokinetics of either trimethoprim or sulfamethoxazole to a clinically relevant extent. ... 

In a placebo-controlled study, 6 healthy subjects were given cimetidine 400 mg every 6 hours for 6 days, with a single 960-mg dose of co-trimox-azole (trimethoprim with sulfamethoxazole) on day 6. Although trimethoprim levels were consistently slightly higher in the presence of cimetidine, they were not significantly different. Cimetidine had no effect on the pharmacokinetics sulfamethoxazole. ... 

Co-trimoxazole suspension (trimethoprim 160 mg with sulfamethoxazole 800 mg) was given to 8 healthy subjects, with and without 20 mL of kaolin-pectin suspension. The kaolin-pectin reduced the AUC and the maximum serum levels of the trimethoprim by about 12% and 20%, respectively. Changes in the sulfamethoxazole pharmacokinetics were not significant. The probable reason for this reduction in AUC is that trimethoprim is adsorbed onto the kaolin-pectin, which reduces the amount available for absorption. However, the reductions are small and unlikely to be clinically relevant. 

Trimethoprim 150 mg twice daily for 7 days prolonged the elimination half-life of a single intravenous 500-mg dose of tolbutamide by 19% in a study in 7 healthy subjects. ... 

Co-trimoxazoie (Trimethoprim/Sulfamethoxazole). The manufacturers note that there was no pharmacokinetic interaction between adefovir 10 mg once daily and co-trimoxazole 960 mg twice daily in 18 heallhy subjects. ... 

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. ... 

A study in 12 healthy subjects given indinavir 400 mg every 6 hours with co-trimoxazole 960 mg every 12 hours found that there was no ehange in the AUC of indinavir, but a small 17% decrease in indinavir trough levels. In addition, there was an 18% increase in the AUC of trimethoprim, and a 5% increase in the AUC of sulfamethoxazole. None of these changes were considered to be clinically important. ... 

Ritonavir 500 mg twice daily caused a 20% increase in the AUC of trimethoprim and a 20% decrease in the AUC of sulfamethoxazole when a single 960-mg dose of co-trimoxazole was given to 15 healthy subjects. These changes were considered too small to be of clinical relevance. The pharmacokinetics of ritonavir were not assessed. 

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. 

The subject of trimethoprim-induced hypersensitivities is not straightforward in that the literature leaves one with the impression that the real situation may not be in full view. From the authors ... 

Thyssen A, Cleton A, Talluri K, Leempoels J, Janssens L, Boom S, Eerdekens M. No pharmacokinetic interaction between paliperidone extended-release tablets and trimethoprim in healthy subjects. Hum Psychopharmacol 2009 24(7) 532-9. 

Toxoplasmosis - This subject was reviewed.73 he cat was implicated as the definitive host of Toxoplasma gondii with small mammals and birds as essential intermediate hosts.73 The therapeutic effect of several sulfa drugs and DDS, alone and in combination with pyrimethamine or trimethoprim, in T. gondii-infected mice was reported. The effect can be reversed by p-aminobenzoic acid, and trimethoprim alone has no activity.T. gondii infections in mice have been cured by clindcimycin and N-demethyl-4 -pentyl clindamycin 6 and by sulfameter plus pyrimethamine or spiramycin.77... 

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