Pharmacological action
Antibacterial agent. Trimethoprim is active against Gram-negative (Escherichia coli, Proteus, Klebsiella) and some gram-positive microorganisms, bacteriostatic effect. The mechanism of action is associated with inhibition of dihydrofolate reductase enzyme in the synthesis of tetrahydrofolic acid.
Pharmacokinetics
Absorption from the gastrointestinal tract quickly and almost complete (90-100%). Plasma protein binding is 45%. C max is achieved within 1-4 h (after a single dose is about 1 mg / ml). Rapidly distributed in tissues and body fluids, including kidneys, liver, spleen, sputum, saliva and semen, is also found in bile, bone marrow and spongy, but not a compact layer of bone. Concentration in the cerebrospinal fluid is 30-50% of serum concentrations. Concentration in tissue and secret prostate is 2-3 times higher concentrations in blood serum. Trimethoprim crosses the placental barrier, penetrates into breast milk. V d in adults 1.3-1.8 l / kg in infants - 2.7 l / kg in children aged 1 to 10 years - 1 l / kg. Metabolised in the liver (10-20% - to inactive metabolites). T 1 / 2 in adults with normal renal function - 8-10 h, in patients with anuria - 20-50 h in newborns - 19 h, in children aged 1 to 10 years - 3-5.5 hours urinary 50-60% within 24 h, mainly by glomerular filtration and tubular secretion, with 80-90% - unchanged, the rest - in the form of inactive metabolites. A small amount (4%) is excreted in the bile. Removing increases with acidic urine and decreases in alkaline. In hemodialysis removed a moderate amount, peritoneal dialysis is ineffective.
Statement
Treatment and prevention of bacterial urinary tract infections caused by susceptible to trimethoprim in drinking water.
Dosage regimen
Inside adults - 40-60 mg 1 time / day, maximum daily dose - 100 mg. For children over 1 year - 2-3 mg / kg 1 time / day.
Side effect
From the CNS: headache, aseptic meningitis.
On the part of the hemopoietic system: methemoglobinemia, agranulocytosis, leukopenia, thrombocytopenia, anemia.
Dermatological reactions: skin rashes, malignant exudative erythema (Stevens-Johnson syndrome).
On the part of the digestive system: diarrhea, anorexia, nausea or vomiting, stomachalgia.
From the urinary system: nephropathy.
Contraindications
Expressed infringements of function of liver and kidney, deficiency of folic acid, pregnancy, megaloblastic anemia due to lack of folic acid during lactation, increased sensitivity to trimethoprim.
Application of pregnancy and breastfeeding
Trimethoprim is contraindicated during pregnancy and lactation (breastfeeding).
Cautions
With careful use, with a possible deficit of folic acid, aggravated by allergy history, asthma, abnormal liver function and thyroid gland in early childhood.
Prolonged use should be systematically study the peripheral blood, the functional state of liver and kidney. Elderly patients showed additional purpose of folic acid.
Drug Interactions
The combination of sulfamethoxazole mutually enhances antimicrobial activity (bactericidal effect).
Myelotoxicity drugs increase the risk of further oppression of the bone marrow. With simultaneous use of cyclosporine increased the frequency of nephrotoxicity.
When applied simultaneously with dapsone may increase the concentrations of both dapsone (may increase the frequency and severity of side effects, especially methemoglobinemia), and trimethoprim, which may be associated with suppression of metabolism of dapsone, and / or competition between two drugs for excretion by the kidneys.
Other folic acid antagonists (methotrexate, pyrimethamine) with simultaneous admission increases the risk of megaloblastic anemia.
Trimethoprim inhibits the hepatic metabolism of phenytoin, increasing its T 1 / 2 by 50% and reducing its clearance by 30%.
Trimethoprim decreases the renal clearance of procainamide and its metabolite N-acetyl-p-aminophenol, increasing their concentration in blood plasma.
When applied simultaneously enhances excretion and shortens the T 1 / 2 rifampin.
Trimethoprim enhances the anticoagulant effect of warfarin due to suppression of its metabolism.
Antibacterial agent. Trimethoprim is active against Gram-negative (Escherichia coli, Proteus, Klebsiella) and some gram-positive microorganisms, bacteriostatic effect. The mechanism of action is associated with inhibition of dihydrofolate reductase enzyme in the synthesis of tetrahydrofolic acid.
Pharmacokinetics
Absorption from the gastrointestinal tract quickly and almost complete (90-100%). Plasma protein binding is 45%. C max is achieved within 1-4 h (after a single dose is about 1 mg / ml). Rapidly distributed in tissues and body fluids, including kidneys, liver, spleen, sputum, saliva and semen, is also found in bile, bone marrow and spongy, but not a compact layer of bone. Concentration in the cerebrospinal fluid is 30-50% of serum concentrations. Concentration in tissue and secret prostate is 2-3 times higher concentrations in blood serum. Trimethoprim crosses the placental barrier, penetrates into breast milk. V d in adults 1.3-1.8 l / kg in infants - 2.7 l / kg in children aged 1 to 10 years - 1 l / kg. Metabolised in the liver (10-20% - to inactive metabolites). T 1 / 2 in adults with normal renal function - 8-10 h, in patients with anuria - 20-50 h in newborns - 19 h, in children aged 1 to 10 years - 3-5.5 hours urinary 50-60% within 24 h, mainly by glomerular filtration and tubular secretion, with 80-90% - unchanged, the rest - in the form of inactive metabolites. A small amount (4%) is excreted in the bile. Removing increases with acidic urine and decreases in alkaline. In hemodialysis removed a moderate amount, peritoneal dialysis is ineffective.
Statement
Treatment and prevention of bacterial urinary tract infections caused by susceptible to trimethoprim in drinking water.
Dosage regimen
Inside adults - 40-60 mg 1 time / day, maximum daily dose - 100 mg. For children over 1 year - 2-3 mg / kg 1 time / day.
Side effect
From the CNS: headache, aseptic meningitis.
On the part of the hemopoietic system: methemoglobinemia, agranulocytosis, leukopenia, thrombocytopenia, anemia.
Dermatological reactions: skin rashes, malignant exudative erythema (Stevens-Johnson syndrome).
On the part of the digestive system: diarrhea, anorexia, nausea or vomiting, stomachalgia.
From the urinary system: nephropathy.
Contraindications
Expressed infringements of function of liver and kidney, deficiency of folic acid, pregnancy, megaloblastic anemia due to lack of folic acid during lactation, increased sensitivity to trimethoprim.
Application of pregnancy and breastfeeding
Trimethoprim is contraindicated during pregnancy and lactation (breastfeeding).
Cautions
With careful use, with a possible deficit of folic acid, aggravated by allergy history, asthma, abnormal liver function and thyroid gland in early childhood.
Prolonged use should be systematically study the peripheral blood, the functional state of liver and kidney. Elderly patients showed additional purpose of folic acid.
Drug Interactions
The combination of sulfamethoxazole mutually enhances antimicrobial activity (bactericidal effect).
Myelotoxicity drugs increase the risk of further oppression of the bone marrow. With simultaneous use of cyclosporine increased the frequency of nephrotoxicity.
When applied simultaneously with dapsone may increase the concentrations of both dapsone (may increase the frequency and severity of side effects, especially methemoglobinemia), and trimethoprim, which may be associated with suppression of metabolism of dapsone, and / or competition between two drugs for excretion by the kidneys.
Other folic acid antagonists (methotrexate, pyrimethamine) with simultaneous admission increases the risk of megaloblastic anemia.
Trimethoprim inhibits the hepatic metabolism of phenytoin, increasing its T 1 / 2 by 50% and reducing its clearance by 30%.
Trimethoprim decreases the renal clearance of procainamide and its metabolite N-acetyl-p-aminophenol, increasing their concentration in blood plasma.
When applied simultaneously enhances excretion and shortens the T 1 / 2 rifampin.
Trimethoprim enhances the anticoagulant effect of warfarin due to suppression of its metabolism.
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