Sanmol

Sanmol Mechanism of Action

paracetamol

Manufacturer:

PT Sanbe Farma

Distributor:

Macropharma Corp
Full Prescribing Info
Action
Pharmacology: PARACETAMOL (SANMOL) Infusion provides onset of pain relief within 5-10 minutes after the start of administration. The peak analgesic effect is obtained in 1 hour and the duration of this effect is usually 4-6 hours. PARACETAMOL (SANMOL) Infusion reduces fever within 30 minutes after the start of administration with a duration of the antipyretic effect of at least 6 hours.
Pharmacokinetics: Adults: Absorption: Paracetamol pharmacokinetics are linier after a single administration of up to 2 g and after repeated administration during 24 hours.
The bioavailability of paracetamol following infusion of 1 g of Paracetamol 10 mg/mL is similar to that observed following infusion of 2 g propacetamol (containing 1 g of paracetamol). For both these products, peak plasma concentration is obtained as and from the end of infusion. The maximum plasma concentration (Cmax) of paracetamol observed following intravenous infusion of 1 g Paracetamol 10 mg/mL is about 30 μg/mL. About 15 minutes is required to obtain the maximal plasma concentration (Tmax).
The bioavailability of paracetamol following infusion of 500 mg of Paracetamol 10 mg/mL, solution for infusion is similar to that observed following infusion of 1 g propacetamol (containing 500 mg paracetamol). The maximum plasma concentration (Cmax) of paracetamol observed at the end of 15-minutes intravenous infusion of 500 mg of Paracetamol 10 mg/mL, solution for infusion is about 15 μg/mL.
The pharmacokinetics of oral paracetamol (500 mg) and intravenous propacetamol (1 g) were compared in a randomised, double-blind, 2-period crossover study in 12 healthy male subjects. As expected, plasma concentrations of intravenous were significantly higher and obtained earlier, compared to oral administration, however after the first hour and up to 24 hours the plasma concentrations remained similar. (See Figure 1 and Table 1 as follows.)

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Click on icon to see table/diagram/image

Distribution: The volume of distribution of paracetamol is approximately 1 L/kg.
Paracetamol is not extensively bound to plasma proteins.
Following infusion of 2 g propacetamol (equivalent to 1 g of paracetamol) significant concentrations of paracetamol (about 1.5 μg/mL) were observed in the cerebrospinal fluid 20 minutes after infusion.
Metabolism: Paracetamol is metabolised mainly in the liver following two 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 (less than 4%) is metabolised by cytochrome P450 to a reactive intermediate (N-acetyl benzoquinone imine) which, under normal conditions of use, 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. At therapeutic doses, CYP3A4, the major isoform of P450 in human liver, contributes to the production of the cytotoxic metabolite. For very high, supratherapeutic plasma concentrations (1500 mg/L) of paracetamol, the 2E1 and 1A2 isoforms may also be involved.
Elimination: The metabolites of paracetamol are mainly excreted in the urine. 90% of the dose administered is excreted in 24 hours, mainly as glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life is 2.7 hours and total body clearance is 18 L/h.
Neonates and Infants <6 Months of Age: Clinical Trials examining the pharmacokinetics of Paracetamol in neonates and infants <6 months of age are limited. The safety and efficacy of Paracetamol in premature neonates has not been established. In a trial of 12 children between 1 and 232 days of age, which included 5 children less than 10 days of age the pharmacokinetics results for Paracetamol were as follows: See Figure 2 and Table 2.

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

In neonates, the plasma half-life is longer than infant's i.e. around 3.5 hours. Neonates and infants excrete significantly less glucuronide and more sulphate conjugates than adults. The potential effect of immaturity in metabolic and elimination pathways of paracetamol should be considered when administering paracetamol to neonates and children <6 months age.
Infants and Children >6 Months of Age: The pharmacokinetic parameters of paracetamol observed in infants and children are similar to those observed in adults, except for the plasma half-life that is slightly shorter (1.5 to 2 h) than in adults.
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