Klacid Hp Mechanism of Action

Pharmacology: Helicobacter pylori is a spiral, flagellated, gram-negative rod, primarily colonising the antrum of the stomach, it congregates at and around intercellular junctions. The natural habitat of H. pylori is the gastric mucosa, where the bacterium attaches itself via adhesion pedestals. H. pylori is associated with duodenal and gastric ulcer disease in about 95% and 70% of patients, respectively. H. pylori is the major factor in the development of gastritis and ulcers in such patients. Eradication of H. pylori is associated with reduced peptic ulcer recurrence. Eradication of H. pylori is therefore appropriate therapy in most patients with duodenal and gastric ulcer where the latter is not caused by nonsteroidal anti-inflammatory drug (NSAID) ingestion. Eradication of H. pylori was achieved in approximately 95% of patients following therapy with clarithromycin, pantoprazole and amoxicillin.
Klacid: Clarithromycin is active in vitro and in vivo against H. pylori. Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible bacteria and suppresses protein synthesis. The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. The minimum inhibitory concentrations (MICs) of this metabolite are equal or 2-fold higher than the MICs of the parent compound.
Controloc: An irreversible proton pump inhibitor which has been developed for the treatment of acid-related gastrointestinal disorders. Pantoprazole reduces gastric acid secretion through inhibition of the proton pump on the gastric parietal cell. As a weak base, pantoprazole is highly ionised at low pH and readily accumulates in the highly acidic canalicular lumen of the stimulated parietal cell. In this acidic environment, pantoprazole is rapidly converted to the active species, a cationic cyclic sulfonamide which binds covalently to cysteine residues on the luminal (acidic) surface of H⁺K⁺-ATPase to form a mixed disulfide, thereby causing irreversible inhibition of gastric proton pump function. As H⁺K⁺-ATPase represents the final step in the secretory process, inhibition of this enzyme suppresses gastric acid secretion regardless of the primary stimulus.
Ospamox: Amoxicillin is a highly potent, broad-spectrum penicillin with a particularly rapid onset and a broad spectrum of action (active against both gram-positive and gram-negative microorganism). Like other penicillins, it acts by inhibiting cell wall synthesis.
Pharmacokinetics: A summary of the pharmacokinetic parameters for Klacid Hp are provided in the following table. For further information regarding pharmacokinetics of Klacid, Controloc or Ospamox, refer to full product information for the appropriate component. (See table.)

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Klacid: Clarithromycin is rapidly and well absorbed from the gastrointestinal tract after oral administration of Klacid tablets. The microbiologically active metabolite 14-hydroxyclarithromycin is formed by first-pass metabolism. Klacid may be given without regard to meals as food does not affect the extent of bioavailability of Klacid tablets. Food does slightly delay the onset of absorption of clarithromycin and formation of the 14-hydroxy metabolite. The pharmacokinetics of clarithromycin are nonlinear; however, steady state is attained within 2 days of dosing. At 250 mg twice daily, 15-20% of unchanged drug is excreted in the urine. With 500 mg twice-daily dosing, urinary excretion is greater (approximately 36%). The 14-hydroxyclarithromycin is the major urinary metabolite and accounts for 10-15% of the dose. Most of the remainder of the dose is eliminated in the faeces, primarily via the bile; 5-10% of the parent drug is recovered from the faeces.
Klacid provides tissue concentrations that are several times higher than the circulating drug levels. Increased levels have been found in both tonsillar and lung tissue. Klacid also penetrates the gastric mucus. Levels of clarithromycin in gastric mucus and gastric tissue are higher when clarithromycin is co-administered with proton pump inhibitor than when clarithromycin is administered alone.
Controloc: Pantoprazole is subjected to low first-pass hepatic extraction, as reflected in an estimated absolute oral bioavailability of 77%. Concomitant intake of food has no influence on the bioavailability of pantoprazole. Plasma pantoprazole concentrations decline monophasically after oral administration with a mean plasma terminal elimination half-life of 0.9-1.9 hrs. Despite the short half-life of pantoprazole, inhibition of acid secretion, once accomplished, is long-lasting, persisting long after the drug has been cleared from the circulation. On repeated (7 days) oral administration, the pharmacokinetics of pantoprazole (20 and 40 mg/day) do not differ appreciably from those on single-dose administration suggesting that drug accumulation does not occur. In keeping with its high degree of plasma protein-binding (98%), pantoprazole has a relatively low apparent volume of distribution (mean 0.16 L/kg at steady state), suggesting limited tissue distribution. Pantoprazole is subject to extensive hepatic metabolism via cytochrome P-450 (CYP)-mediated oxidation followed by sulfate conjugation. Elimination is renal, with 80% of an oral dose being excreted as urinary metabolites, the remainder is excreted in the faeces which originates primarily from biliary secretion. The pharmacokinetics of pantoprazole do not appear to be modified to any clinically relevant extent by renal impairment. Haemodialysis does not appear to significantly influence the pharmacokinetics of pantoprazole or its main metabolite M2 in patients with renal disease or end-stage renal failure. The metabolism of pantoprazole is impaired in patients with hepatic dysfunction. However, C_max was only marginally elevated (50%), indicating that pantoprazole may be given without dosage adjustment to patients with hepatic impairment.
Ospamox: The absorption of amoxicillin is unaffected by meals. The drug is almost completely absorbed from the small intestine. Peak serum levels are reached within 1-2 hrs after ingestion. Amoxicillin readily distributes in body tissues and fluid including the sputum and purulent bronchial secretions. If liver function is intact, high biliary drug concentrations are reached. Amoxicillin is eliminated at a half-life of approximately 1-2 hrs. Elimination is predominantly renal. More than half of the oral dose is excreted with the urine in a therapeutically active form.