Proton pump inhibitor
Controloc: contains Pantoprazole, a proton pump inhibitor which inhibits the gastric H+K+ ATPase which is responsible for acid secretion in the parietal cells of the stomach. Pantoprazole is a white to off-white powder with a molecular weight of 432.4. Pantoprazole is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. Pantoprazole is a racemic mixture with a melting point of 138° C. The chemical name for Pantoprazole is sodium 5- (difluoromethoxy)-2-[[(3,4dimethoxy-2-pyridinyl)methyl]sulfinyl]-IH-benzimidazole sesquihydrate and is represented by the following chemical structure:
Empirical chemical structure : C16H14F2N3NaO4Sxl.5H2O
Name and Strength of Active ingredient
Pantoprazole sodium sesquihydrate 22.6 mg (equivalent to pantoprazole 20 mg)
Sodium carbonate; mannitol; crospovidone; povidone K 90; calcium stearate; hypromellose; povidone K 25; propylene glycol; methacrylic acid-ethylacrylate- copolymer (1:1); polysorbate 80; sodium laurylsulphate; triethyl citrate: colours (E 171 and E 172); printing ink
Pharmacotherapeutic / indication group / action mechanism
Selective proton pump inhibitor, substituted benzimidazole
Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific action on the proton pumps of the parietal cells. Pantoprazole is converted to its active form in the acidic canaliculi of the parietal cells where it inhibits the H+, K+ - ATPase enzyme, i.e. the final stage in the production of hydrochloric acid in the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, freedom from symptoms is achieved in 2 weeks. As with other proton pump inhibitors and H receptor inhibitors, treatment with pantoprazole causes a reduced acidity in the stomach and thereby an increase in gastrin in proportion to the reduce in acidity. The increase in gastrin is reversible.
Since pantoprazole binds to the enzyme distal to the cell receptor level, the substance can affect hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the products are given orally or intravenously.
The fasting gastrin values increase under pantoprazole. On short-term use, in most cases they do not exceed the normal upper limit During long-term treatment, gastrin levels double in most cases. An excessive increase, however, occurs only in isolated cases. As a result, a mild to moderate increase in the number of specific endocrine (ECL) cells in the stomach is observed in a minority of cases during long-term treatment (simple to adenomatoid hyperplasia). However, according to the studies conducted so far, the formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids as were found in animal experiments can be ruled out for humans for a
1 -year treatment period.
An influence of a long term treatment with pantoprazole exceeding one year cannot be completely ruled out on endocrine parameters of the thyroid and liver enzymes according to results in animal studies.
Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single 20 mg oral dose. On average at about 2.0 h - 2.5 h p.a. the maximum serum concentrations of about
1-1.5 µg/ml are achieved, and these values remain constant after multiple administration. Volume of distribution is about 0.15
l/kg and clearance is about 0.1 l/h/kg.
Terminal half-life is about 1 h. There were a few cases of subjects with delayed elimination. Because of the specific binding of pantoprazole to the proton pumps of the parietal cell the elimination half-life does not correlate with the much longer duration of action (inhibition of acid secretion).
Pharmacokinetics do not vary after single or repeated administration. In the dose range of 10 to 80 mg, the plasma kinetics of pantoprazole are linear after both oral and intravenous administration.
Pantoprazole's serum protein binding is about 98%.
Pantoprazole is completely absorbed after oral administration. The absolute bioavailability from the tablet was found to be about 77%. Concomitant intake of food had no influence on AUC, maximum serum concentration and thus bioavailability. Only the variability of the lag-time will be increased by concomitant food intake.
The substance is almost exclusively metabolized in the liver. Renal elimination represents the major route of excretion (about 80%) for the metabolites of pantoprazole, the rest is excreted with the faeces. The main metabolite in both the serum and urine is desmethylpantoprazole which is conjugated with sulphate. The half-life of the main metabolite (about 1.5 h) is not much longer than that of pantoprazole.
Characteristics in patients/special groups of subjects
No dose reduction is requested when pantoprazole is administered to patients with restricted kidney function (including dialysis patients). As with healthy subjects, pantoprazole's half-life is short Only very small amounts of pantoprazole can be dialyzed. Although the main metabolite has a moderately delayed half-life (2 - 3h), excretion is still rapid and thus accumulation does not occur.
Although for patients with liver cirrhosis (classes A and B according to child) the half-life values increased to between 3 and 6 h and the AUC values increased by a factor of 3 - 5, the maximum serum concentration only increased slightly by a factor of 1.3 compared with healthy subjects.
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is also not clinically relevant.
Following administration of single oral doses of 20 or 40 mg pantoprazole to children aged 5-16 years AUC and Cmax were in the range of corresponding values in adults. Following administration of single i.v. doses of 0.8 or 1.6 mg/ kg pantoprazole to children aged 2-16 years there was no significant association between pantoprazole clearance and ag or weight, AUC and volume of distribution were in accordance with data form adults.