Infulgan Mechanism of Action

Pharmacotherapeutic Group: Analgesics and antipyretics. ATC Code: N02BE01.
Pharmacology: Pharmacodynamics: Infulgan (paracetamol) exhibits analgesic and antipyretic properties. Paracetamol affects the site of pain and the heat-regulating center by blocking cyclooxygenase (COX) I and II only in central nervous system. Cell peroxidase neutralizes paracetamol effect on COX in irritated tissues that results in complete absence of any anti-inflammatory effect. No effect on prostaglandin synthesis in peripheral tissues stipulates the absence of negative impact on water-salt metabolism and gastrointestinal mucosa.
Pharmacokinetics: Concentration of paracetamol in plasma reaches its peak in 15 minutes. Maximum concentration is 15-30 µg/mL. Distribution volume is 1 L/kg. Plasma protein binding of paracetamol is negligible. Paracetamol passes blood-brain barrier. It is metabolised in the liver by conjugation to glucuronides and sulphates. A small amount (4%) is metabolised by cytochrome P450 to an intermediate metabolite (N-acetyl benzoquinon imine) which is rapidly detoxified by reconstituted glutathione and eliminated with urine after conjugation with cysteine and mercapturic acid under the normal conditions. However, in case of massive overdosing the quantity of this toxic metabolite grows. Elimination half-life is 2.7 hours in adult, 1.5 to 2 hours in children, and 3.5 hours in infants. Total body clearance is 18 L/h. Paracetamol is mainly eliminated with urine. 90% of the administrated dose is excreted by kidneys within 24 hours as glucuronide (60-80%) and sulphate (20-30%) predominantly. Less than 5% is excreted unchanged. Paracetamol elimination is slightly delayed in patients with severe renal insufficiency (creatinine clearance less than 10-30 mL/min). Elimination half-life in this case varies from 2 to 5.3 hours. Elimination rate of glucuronide and sulphate in patients with severe renal insufficiency is 3 times slower than in healthy volunteers.
Pediatric pharmacokinetics is generally similar to that in adults except for the plasma elimination half-life that is slower (1.5-2 hours). Conjugation to glucuronic acid is significantly reduced and conjugation to sulphate is increased in children up to 10 years compared to adults.