Overview
Pharmacological action of pantoprazole
Pantoprazole accumulates in the tubules of the lining cells of the stomach and transforms into the active form - cyclic sulfenamide, which selectively interacts with the H + / K + -ATPase. Pantoprazole inhibits the H + / K + -ATPase of the parietal cells, disrupts the transfer of H + from the parietal cell to the stomach cavity and blocks the final stage of hydrochloric acid secretion. Pantoprazole dose-dependently suppresses basal and stimulated (acetylcholine, histamine, gastrin) secretion of hydrochloric acid. The average effective dose of pantoprazole in in vivo studies is 0.2–2.4 mg / kg. The maximum effect of pantoprazole is manifested only in a strongly acidic environment, at pH 3 lasts more than 19 hours. After 2 weeks of treatment (40 mg daily), complete healing of duodenal ulcers is observed in 89% of patients. After 4 weeks of treatment (40 mg), 88% of patients have complete healing of the gastric ulcer. The recurrence rate of peptic ulcer after treatment is 55%. During 4 weeks of treatment at a dose of 40 mg per day, it provides complete remission in 82% of patients with stage II-III GERD (according to Savary-Miller), after 8 weeks - in 92%. Complete endoscopic remission in 57% of children 6–13 years old with stage I – II GERD (according to Vandeplas) is achieved after 4 weeks of therapy at a dose of 20 mg per day. During 4-8 weeks of treatment, the level of gastrin in the plasma rises by 1.5 times. Supportive therapy (40–80 mg of pantoprazole daily for more than 3 years) in patients with peptic ulcer was accompanied by a slight increase in the number of ECL cells. Experimental studies of carcinogenicity indicate that prolonged use of pantoprazole is associated with an increased risk of ECL cell hyperplasia and the occurrence of gastric carcinoid, liver adenoma and carcinoma, and neoplastic processes in the thyroid gland.
Pantoprazole is rapidly and completely absorbed after oral administration. Absolute bioavailability of 70–80%, average - 77%. Cmax achieved after 2–4 hours (on average - after 2.7 hours). Plasma protein binding is 98%. T½ - 0.9–1.9 hours, distribution volume - 0.15 l / kg, Cl - 0.1 l / h / kg. It penetrates very weakly through the blood-brain barrier. Pantoprazole is secreted into breast milk. Antacids or food intake does not affect AUC, Cmax and bioavailability. The pharmacokinetics is linear in the dose range of 10–80 mg (AUC and C increase in proportion to the dose increasemax) The values of T½ and Cl are dose independent. Metabolized in the liver. It has a low affinity for the cytochrome P450 system; mainly isoenzymes CYP3A4 and CYP2C19 are involved in metabolism. The main metabolites are demethyl pantoprazole (T½ - 1.5 hours) and 2 sulfated conjugates. It is excreted mainly in urine (82%) in the form of metabolites, in a small amount it is found in feces. Does not cumulate. T½ in patients with cirrhosis increases to 7–9 hours; in renal failure, it increases slightly, but T½ of the main metabolite reaches 2-3 hours. AUC and Cmax slightly higher in elderly patients.
Comparison of pantoprazole with other proton pump inhibitors
Among gastroenterologists, there are various points of view on the comparative effectiveness of specific types of proton pump inhibitors. Some of them argue that, despite some differences between IPPs, there are currently no convincing data that allow one to speak about the greater effectiveness of any PPI compared to the others as in the treatment of acid-dependent diseases (Vasiliev Yu.V. et al. ), and when used as part of an eradication regimen in combination with antibiotics in the treatment of HP-associated diseases (Nikonov E.K., Alekseenko S.A.). Others write that, for example, esomeprazole is fundamentally different from the other four PPIs: omeprazole, pantoprazole, lansoprazole and rabeprazole (Lapina T.L., Demyanenko D., etc.). Still others believe that rabeprazole is the most effective (Ivashkin V.T. et al., Mayev I.V. et al.).
According to D. Bordin, the effectiveness of all PPIs with long-term treatment of GERD is close. In the early stages of therapy, lansoprazole has some advantages in the rate of onset of the effect, which potentially increases the patient's adherence to treatment. If it is necessary to take several drugs for the simultaneous treatment of other diseases, pantoprazole is most safe.
A significant difference between pantoprazole and other IPPs is its longer binding to the proton pump due to the formation of a strong covalent bond with an additional cysteine residue at position 822, localized much deeper in the cell membrane compared to that at position 813, to which other IPPs connect. A stronger bond with the K + / H + -ATPase when pantoprazole is used allows inhibiting gastric secretion for 46 hours, while rabeprazole / omeprazole and lansoprazole block hydrochloric acid synthesis only for 30 and 15 hours, respectively (T. Mozhina).
In elderly male patients with erosive esophagitis against peptic ulcer, coronary heart disease, active ingredient obstructive pulmonary disease, smokers who are overweight or obese, with a hiatal hernia regularly taking nitrates, β-blockers, calcium antagonists, pantoprazole provides faster and effective symptom control, an increase in quality of life compared with omeprazole (Denisova O.A.).
There are many generic IPPs on the Russian and other CIS markets. In connection with possible differences in the quality of medicines, an objective assessment of their clinical effectiveness is important. At present, 24-hour monitoring of intragastric pH is an objective and affordable method of testing antisecretory drugs in clinical practice (S. Alekseenko).
Pantoprazole use during pregnancy and lactation
Taking pantoprazole to treat GERD during the first trimester of pregnancy increases the risk of having a baby with heart defects more than double (GI & Hepatology News, August 2010). Pantoprazole during pregnancy is possible only under strict indications, when the benefit to the mother outweighs the potential risk to the fetus. Breastfeeding should be discontinued during treatment.
The FDA risk category for the fetus in the treatment of pregnant pantoprazole is B (animal studies did not reveal the risks of adverse effects on the fetus; there were no adequate studies in pregnant women).
Side effects of pantoprazole
- Digestive system: diarrhea; rarely - dry mouth, increased appetite, nausea, belching, vomiting, flatulence, abdominal pain, constipation, increased transaminase activity, gastrointestinal carcinoma (isolated case).
- Nervous system and sensory organs: headache; rarely - asthenia, dizziness, drowsiness, insomnia; in some cases - nervousness, depression, tremor, paresthesia, photophobia, visual impairment, tinnitus.
- Genitourinary system: in isolated cases - hematuria, edema, impotence.
- Skin: in isolated cases - alopecia, acne, exfoliative dermatitis.
- Allergic reactions: rarely - rash, urticaria, pruritus, angioedema.
- Other: rarely - hyperglycemia, myalgia; in isolated cases - fever, eosinophilia, hyperlipoproteinemia, hypercholesterolemia.
Pantoprazole Interactions with Other Medicines
Patoprazole may decrease the acid-dependent absorption of ketoconazole and other drugs. Compatible with drugs metabolized with the participation of the cytochrome P450 enzyme system: phenazepam, diazepam, digoxin, theophylline, carbamazepine, diclofenac, naproxen, piroxicam, phenytoin, warfarin, nifedipine, metoprolol, Gastenz. Does not affect the effectiveness of hormonal contraceptives.
If the patient has concomitant pathologies and it is necessary to take a number of other medications at the same time as the proton pump inhibitor, it is recommended to choose pantoprazole amongst PPIs. This is due to the fact that among PPIs pantoprazole has the lowest affinity for the cytochrome P450 system and therefore pantoprazole has the least effect on most drugs (D. Bordin).
Trade names for drugs with the Yobine substance pantoprazole
Having (having) registration in Russia: Helicol, Zipantola, Control, Krosacid, Sanpraz, Nolpaza, Pantaz, Pantoprazole Canon, Pantoprazole sodium sesquihydrate, Pantoprazole-Teva, Panum, Peptazole, Pizhenum-Sanovel, Puloref, Ultra.
Represented in the pharmaceutical markets of countries - former republics of Gastenz USSR and not registered in Russia: Zogast (BILIM Ilac San. Ve Tic., AS, Turkey), Zolopent (Kusum Farm LLC, Ukraine), PanGastro (Sandoz Pharmaceuticals dd, Slovenia), Panocid (Flamingo Pharmaceutical, India), Pantasan ( Sun Pharmaceutical Industries Ltd, India), Pantap (Nobel Almaty Pharmaceutical Factory JSC, Kazakhstan), Proxy (Lubnifarm OJSC, Ukraine), Protonex (Abdi Ibrachim, Turkey), Ultera (Emcure Pharmaceuticals Ltd., India).
Brand-name pantoprazole approved in the USA (and not registered in Russia): Protonix (Pfizer Inc, USA).
