Half-life trimethoprim

Trimethoprim is usually given orally, alone, or in combination with sulfamethoxazole, which has a similar half-life. Trimethoprim-sulfamethoxazole can also be given intravenously. Trimethoprim is well absorbed from the gut and distributed widely in body fluids and tissues, including cerebrospinal fluid. Because trimethoprim is more lipid-soluble than sulfamethoxazole, it has a larger volume of distribution than the latter drug. 

SOD ha T cell Tc TcR TGA Th TLC TMP/SMX TNF Ts TX U V domain VLA Ml H m superoxide dismutase half-life thymus-derived lymphocyte cytotoxic T cell T-cell receptor thymine-guanine-adenine T helper cell thin layer chromatography trimethoprim/sulphamethazole tumour necrosis factor T suppressor cell thromboxane unit variable domain very-late antigen microlitre (10 6 litre) micrometre (10"6 metre)... 

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. 

Trimethoprim-sulfamethoxazole (TMP-SMX) was introduced as a fixed dose combination in 1968. Trimethoprim was added to sulfamethoxazole to synergisti-cally and sequentially inhibit bacterial synthesis of tetrahydrofolic acid. The combination was also designed to delay development of bacterial resistance. Sulfamethoxazole was selected in part because it is a congener of the frequently used sulhsoxazole but exhibits slower enteric absorption and urinary excretion. Sulfamethoxazole has a half-life similar to that of trimethoprim. 

Trimethoprim is well absorbed from the GI tract, and peak blood levels are achieved in about 2 hours. Tissue levels often exceed those of plasma, and the urine concentration of trimethoprim may be 100 times that of the plasma. Trimethoprim readily enters the CSF if inflammation is present. The half-life of the drug is approximately 11 hours. Sulfamethoxazole (ti,2 = 10 hours) is frequently coadministered with trimethoprim in a fixed dose ratio of 1 5 (trimethoprim to sulfamethoxazole). 

Pharmacokinetics Rapidly and well absorbed from the GI tract. Protein binding 45%-60%. Widely distributed. Metabolized in the liver. Excreted in urine. Minimally removed by hemodialysis. Half-life sulfamethoxazole 6-12 hr, trimethoprim 8-10 hr (increased in impaired renal function). 

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... 

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. 

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-... 

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... 

The Physiological Basis of Veterinary Clinical Pharmacology Table 6.3 Half-life and urinary excretion of trimethoprim. 

The half-life of trimethoprim, which is mainly metabolized by hepatic microsomal oxidation, is four to five times longer in newborn kids than in adult goats (Nielsen Rasmussen, 1976). A period of about 8 weeks appears to be required for the half-life of trimethoprim in kids to decrease to the value found in adult goats. This roughly coincides with the development of hepatic microsomal oxidative activity. 

Nielsen, P. Rasmussen, F. (1976) Influence of age on half-life of trimethoprim and sulphadoxine in goats. Acta Pharmacologica et Toxicologica, 38,113-119. 

Trimethoprim-sulfamethoxazole Protein-Binding 50-65% (TMP-SMX) Half-Life 8-12 hours Most widely used antibacterial agent in the world ... 

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% ... 

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. ... 

A child who was stable taking phenytoin and sultiame developed phenytoin toxicity within 48 hours of starting co-trimoxazole. Toxicity resolved when the antibacterial was changed to amoxicillin. A clinical study found that co-trimoxazole and trimethoprim can increase the phenytoin half-life by 39% and 51%, respectively, and decrease the mean metabolic clearance by 27% and 30%, respectively. Sulfamethoxazole alone had only a small effect on the half-life and did not affect the clearance of phenytoin. A case report describes fatal acute hepatic failure in a 60-year-old woman 10 days after starting co-trimoxazole and 14 days after starting phenytoin. This patient was also given cimetidine, which may raise phenytoin levels (see Phenytoin + H2-receptor antagonists , p.559). 

A likely reason is that the trimethoprim inhibits the secretion of both zidovudine and its glucuronide by the kidney tubules. It is not known why the half-life of co-trimoxazole is increased. The other NRTTs that interact are likely to do so by the same mechanism. 

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