Ifimol IV Mechanism of Action

Pharmacology: Pharmacokinetics: Absorption: Paracetamol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hrs. The maximal plasma concentration (C_max) of paracetamol is observed at the end of 15 min. Intravenous infusion of 500 mg and 1 g is about 15 mcg/mL and 30 mcg/mL, respectively.
Distribution: The volume of distribution of paracetamol is approximately 1 L/kg.
Paracetamol is not extensively bound to plasma proteins.
Following infusion of 1 to plasma proteins of paracetamol (about 1.5 mcg/mL) were observed in the cerebrospinal fluid at and after the 20th min following infusion.
Metabolism: Paracetamol is metabolised mainly in the liver following 2 major hepatic pathways: Glucuronic acid conjugation and sulphuric acid conjugation. The latter route is rapidly saturable at doses that exceed the therapeutic doses. A small fraction (<4%) is metabolised by cytochrome P450 to a reactive intermediate (N-acetyl benzoquinone imine), which under normal conditions uses, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugation with cysteine and mercapturic acid. However, during massive overdosing, the quantity of this toxic metabolite is increased.
Elimination: The metabolites of paracetamol are mainly excreted in the urine. Ninety percent (90%) of the dose administered is excreted within 24 hrs, mainly in glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life (t_½) is 2.7 hrs and total body clearance is 18 L/hr.
Special Population: Neonates, Infants and Children: The pharmacokinetic parameters of paracetamol observed in infants and children are similar to those observed in adults, except for the plasma t_½ that is slightly shorter (1.5-2 hrs) than in adults. In neonates, the plasma t_½ is longer than in infants ie, around 3.5 hrs. Neonates, infants and children up to 10 years excrete significantly less glucuronide and more sulphate conjugates than adults.
Renal Insufficiency: In cases of severe renal impairment [creatinine clearance (CrCl) 10-30 mL/min), the elimination of paracetamol is slightly delayed, the elimination t_½ ranging from 2-5.3 hrs for the glucuronide and sulphate conjugates, the elimination rate is 3 times slower in subjects with severe renal impairment than in healthy subjects. Therefore, when giving paracetamol to patients with severe renal impairment (CrCl 30 mL/min), the minimum interval between each administration should be increased to 6 hrs.
Elderly: The pharmacokinetics and the metabolism of paracetamol is not modified in elderly subjects. No dose adjustment is required in this population.