Pharmacology: Pharmacokinetics: Absorption: Hapacol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hrs. The maximal plasma concentration (Cmax) of Hapacol 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 Hapacol is approximately 1 L/kg.
Hapacol is not extensively bound to plasma proteins.
Following infusion of 1 to plasma proteins of Hapacol (about 1.5 mcg/mL) were observed in the cerebrospinal fluid at and after the 20th min following infusion.
Metabolism: Hapacol 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 Hapacol 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 (t½) is 2.7 hrs and total body clearance is 18 L/hr.
Special Population: Neonates, Infants and Children: The pharmacokinetic parameters of Hapacol observed in infants and children are similar to those observed in adults, except for the plasma t½ that is slightly shorter (1.5-2 hrs) than in adults. In neonates, the plasma t½ 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 Hapacol is slightly delayed, the elimination t½ 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 Hapacol 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 Hapacol is not modified in elderly subjects. No dose adjustment is required in this population.
May be taken with or without food.
The analgesic, antipyretic, and anti-inflammatory effects of aspirin are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Hapacol directly and irreversibly inhibits the activity of both types of cyclo-oxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes aspirin different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Hapacol's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation–inhibiting effect of aspirin specifically involves the compound's ability to act as an acetyl donor to the platelet membrane; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Hapacol affects platelet function by inhibiting the enzyme prostaglandin cyclooxygenase in platelets, thereby preventing the formation of the aggregating agent thromboxane A2. This action is irreversible; the effects persist for the life of the platelets exposed. Hapacol may also inhibit formation of the platelet aggregation inhibitor prostacyclin (prostaglandin I2) in blood vessels; however, this action is reversible.
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Information checked by Dr. Sachin Kumar, MD Pharmacology