240 mg/5 mL SUSPENSION
A N T I B A C T E R I A L

 

FORMULATION:
Each 5 mL (1 teaspoonful) contains:
Sulfamethoxazole, USP…..................................................................................…….200 mg
Trimethoprim ….……...........................................................…....…40 mg

DESCRIPTION:
Cotrimoxazole (Primecotrix) is a synthetic antibacterial combination product containing 200 mg sulfamethoxazole and 40 mg trimethoprim per 5 mL for oral administration. Cotrimoxazole (Primecotrix) is a white to off-white suspension with orange/butterscotch flavor with sweet fruit/candy taste.

PHARMACODYNAMICS:
Cotrimoxazole (Primecotrix) contains Sulfamethoxazole and Trimethoprim which sequentially inhibits two bacterial enzymes that result in successive stage in the biosynthesis of the folinic acid in the microorganisms. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Sulfamethoxazole inhibits the bacterial synthesis of dihydrofolic acid by competing with PABA (Para Amino Benzoic Acid). This result is more in bactericidal activity in vitro at concentrations at which the individual substances are only bacteriostatic. Sulfamethoxazole and Trimethoprim blocks two consecutive steps in the biosynthesis of nucleic acid and proteins essential to many bacteria.

PHARMACOKINETICS:
Absorption:
Trimethoprim and Sulfamethoxazole are completely and rapidly absorbed after oral administration. Following a single dose of 800 mg of Sulfamethoxazole and 160 mg of Trimethoprim, peak plasma concentrations of 40-80 μg/mL of Sulfamethoxazole and 1.5-30 μg/mL of Trimethoprim are reached within 1-4 hours. Following 12-hour interval of repeated above dosage administration, minimum plasma concentration is achieved in 2-3 days at steady state range between 32 μg/mL and 63 μg/mL Sulfamethoxazole and 1.3 μg/mL—2.8 μg/mL Trimethoprim.

Bioavailabilty:
The absolute oral bioavailability of absorption of Sulfamethoxazole and Trimethoprim is complete for reaching 100% of both drugs.

Distribution:
The volume of distribution is approximately 0.2 L/kg for Sulfamethoxazole and 1.6 L/kg for trimethoprim, while the plasma protein binding reaches 66.2% of Sulfamethoxazole and 37% for Trimethoprim. Superior penetration by Trimethoprim, relative to Sulfamethoxazole has been reported in saliva, normal and inflamed lung tissues, bile fluid, vaginal fluid, seminal fluid and non-inflamed prostatic tissue whereas penetration into aqueous humor and cerebrospinal fluid is similar on both compounds.

Metabolism:
Trimethoprim dose is metabolized by 20%. The cytochrome P450 isoenzymes involved in the oxidative metabolism of Trimethoprim have not been identified. The principal Trimethoprim metabolites are 1- and 3-oxides and the 3- and 4- hydroxy derivatives; some metabolites are microbiologically active. Approximately 80% of Sulfamethoxazole is metabolized by the liver, predominantly to the N-4 acetyl derivative and to a lesser extent by glucuronide conjugation. Sulfamethoxazole also undergoes oxidative metabolism. The first step of the oxidative pathway, which leads to the formation of the hydroxylamine derivative is catalyzed by CYP2C9

Elimination:
The elimination half-life of Sulfamethoxazole is 11 hours and for Trimethoprim is 10 hours. The metabolites of Sulfamethoxazole and Trimethoprim are eliminated clearly by the kidneys through glomerular filtration and tubular secretion by giving the urine concentrations of both active substances higher than the blood concentrations. One quarter Sulfamethoxazole and 2/3 of Trimethoprim are excreted unchanged into the urine. The total plasma clearance of Trimethoprim equal 1.9mL/min/kg. The total plasma clearance of Sulfamethoxazole is equal to 0.32 mL/min/kg. Small quantity of Sulfamethoxazole and Trimethoprim are eliminated via feces. Both of their metabolites are eliminated entirely by the kidneys through glomerular filtration and tubular secretion, giving urine concentrations of both active substances considerably higher than the concentration in the blood.

INDICATIONS:
For acute and chronic disorders of upper and lower respiratory tract infections.