1. Treatment of hypertension in patients with peptic ulcer and liver pathology DM Leonid Lazebnik DM Leonid Lazebnik DM Olga Mikheeva The Central Research institute of gastroenterology Russian Federation, Moscow 2010

2. Urgency of the problem Statistics show that the increase in blood pressure is observed in 40% of the population, of which 30% of patients with hypertension combined with the pathology of the liver Statistics show that the increase in blood pressure is observed in 40% of the population, of which 30% of patients with hypertension combined with the pathology of the liver For correction of BP are used antihypertensive drugs of various groups, among which most often appointed are ACE inhibitors For correction of BP are used antihypertensive drugs of various groups, among which most often appointed are ACE inhibitors

3. Pharmacokinetic classification of ACE inhibitors Pharmacologically active drugs (captopril), which are metabolized and converted into active disulfides Pharmacologically active drugs (captopril), which are metabolized and converted into active disulfides Inactive prodrugs converted in the liver to active metabolites (enalapril to enalaprilat), which are then metabolized into inactive compounds Inactive prodrugs converted in the liver to active metabolites (enalapril to enalaprilat), which are then metabolized into inactive compounds Water-soluble drugs (lisinopril), which are not subjected to metabolism and eliminated through the kidneys unchanged Water-soluble drugs (lisinopril), which are not subjected to metabolism and eliminated through the kidneys unchanged

4. Purpose of the study To investigate the pharmacokinetic and pharmacodynamic characteristics of lisinopril in the treatment of patients with arterial hypertension, occurring on the background pathology of the digestive system To investigate the pharmacokinetic and pharmacodynamic characteristics of lisinopril in the treatment of patients with arterial hypertension, occurring on the background pathology of the digestive system

5. Study design The control group consisted of patients with peptic ulcer disease without dysfunction of the liver The control group consisted of patients with peptic ulcer disease without dysfunction of the liver 90 patients with hypertension and pathology of gastrointestinal track control group 30 patients with steatosis of the iver 30 patients 30 patients with cirrhosis 30 patients treatment with lisinopril

6. Indicators of ABPM in the treatment lisinopril 10 mg hypertensive patients with pathology of the digestive According to the ABPM all examined patients initially had increased BP According to the ABPM all examined patients initially had increased BP No significant differences among indicators ABPM hypertensive patients with different pathologies of the digestive system have been identified No significant differences among indicators ABPM hypertensive patients with different pathologies of the digestive system have been identified

7. Indicators of ABPM in hypertensive patients with pathology of the digestive system during treatment with lisinopril 10 mg average daily SBP average daily DBP average daily IT SBP average daily IT DBP мм Hg % % Treatment with lisinopril 10 mg leads to significantly decreased mean BP values, temporary index (IT) BP in most patients, regardless of the severity of liver changes in patients with hypertension

8. The effectiveness (IT BP < 30 %) of monotherapy with lisinopril in hypertensive patients with pathology of the digestive system The effectiveness of therapy lisinopril 10 mg lisinopril 20 mg AH patients with steatosis of the liver effectiveness 50 % 36,7 % AH patients with cirrhosis effectiveness53,3% 33,3 % Control group effectiveness53,3% 30 %

9. The effectiveness of monotherapy with lisinopril in hypertensive patients with pathology of the liver We got a good hypotensive effect in the treatment with lisinopril 10 mg in 53.3% of the patients with cirrhosis. We got a good hypotensive effect in the treatment with lisinopril 10 mg in 53.3% of the patients with cirrhosis. Increasing the dose in half, gave a good effect even in 33,3% of patients Increasing the dose in half, gave a good effect even in 33,3% of patients In 53,3% of patients with hypertension of the control group a good hypotensive effect was achieved when taking 10 mg, 30% of patients - 20 mg of lisinopril per day In 53,3% of patients with hypertension of the control group a good hypotensive effect was achieved when taking 10 mg, 30% of patients - 20 mg of lisinopril per day

10. Pharmacokinetic study We studied the pharmacokinetics after a single dose of lisinopril 10 mg in patients with hypertension and gastrointestinal disorders We studied the pharmacokinetics after a single dose of lisinopril 10 mg in patients with hypertension and gastrointestinal disorders We determined the concentration of lisinopril in serum of patients by high performance liquid chromatography We determined the concentration of lisinopril in serum of patients by high performance liquid chromatography

11. The main pharmacokinetic parameters The area under the curve "concentration - time" (AUC) - an area the figure bounded pharmacokinetic curve and the coordinate axes The area under the curve "concentration - time" (AUC) - an area the figure bounded pharmacokinetic curve and the coordinate axes C max - maximum concentration of drug in serum (ng/ml) C max - maximum concentration of drug in serum (ng/ml) T max - time of maximum concentration of drugs (t) T max - time of maximum concentration of drugs (t) MRT - mean residence time of drugs (t) MRT - mean residence time of drugs (t)

12. Pharmacokinetic parameters of lisinopril 10 mg in hypertensive patients with digestive diseases ng t/ml t t We found that in patients in both groups were observed no differences in pharmacokinetic parameters after taken of 10 mg of lisinopril

13. Pharmacokinetic and pharmacodynamic curves for hypertensive patients with pathology of the digestive system while taking 10 mg of lisinopril concentration of lisinopril Ng/ml t mean BP, mm Hg t Pharmacokinetic parameters did not differ in hypertensive patients depending on the pathology of the gastrointestinal tract

14. Water-soluble lisinopril is not subjected to metabolism of the patient, therefore, its concentration in plasma is determined the dose taken inside Water-soluble lisinopril is not subjected to metabolism of the patient, therefore, its concentration in plasma is determined the dose taken inside Differences of each pharmacokinetic parameter (C max, T max, MRT, AUC) in groups of BP patients with various pathologies of the digestive sistem were statistically insignificant Differences of each pharmacokinetic parameter (C max, T max, MRT, AUC) in groups of BP patients with various pathologies of the digestive sistem were statistically insignificant Pharmacokinetic parameters of lisinopril 10 mg in hypertensive patients with hepatic pathology

15. Conclusion Water-soluble lisinopril initially pharmacologically active form, therefore has an advantage over ACE inhibitors, which are metabolized in the liver Water-soluble lisinopril initially pharmacologically active form, therefore has an advantage over ACE inhibitors, which are metabolized in the liver We observed no differences in pharmacokinetic parameters in patients with BP, both normal and with impaired liver function after taking lisinopril 10 mg We observed no differences in pharmacokinetic parameters in patients with BP, both normal and with impaired liver function after taking lisinopril 10 mg This is expressed in reaching target BP levels in 53,3% of patients in both groups This is expressed in reaching target BP levels in 53,3% of patients in both groups