BACKGROUND: Antihypertensive effect and safety of the newer, long acting, nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril, were studied. METHODS: Twenty eight patients of mild to moderate essential hypertension were administered 10-20mg of lisinopril once daily for ten weeks. Patients were evaluated every two weeks concerning the changes of blood pressure and pulse rate in the sitting position and also any untoward sumptoms and signs attributable to the side effect. Chest X-rey, ECG and laboratory examination were performed in principle two times before and after the completion of medication. RESULTS: The blood pressure declined from 165.4/107.6mmHg to 141.3/92.4mmHg at the end of ten weeks of medication, thus the reduction of 24.1mmHg of systolic pressure and 15.2mmHg of diastolic pressure were observed and the overall effective rate was 85.7%. The pulse rate and laboratory findings were not sigificantly changed before and after the administration of lisinopril. The side effects were observed in 2 cases(7.1%) of mild dry cough and in 2 cases(7.1%) of transitory mild headache and in 1 case(3.6%) of dizziness but no one discontinued medication due to adverse effects. CONCLUSION: Lisinopril proved effective and safe in the treatment of mild to moderate essential hypertension.
Blood Pressure ; Cough ; Dizziness ; Electrocardiography ; Headache ; Heart Rate ; Humans ; Hypertension* ; Lisinopril* ; Peptidyl-Dipeptidase A ; Thorax

During the routine impurity profile of lisinopril bulk drug by HPLC (high-performance liquid chromatography), a potential impurity was detected. Using multidimensional NMR (nuclear magnetic resonance) technique, the trace-level impurity was unambiguously identified to be 2-(-2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid after isolation from lisinopril bulk drug by semi-preparative HPLC. Formation of the impurity was also discussed. To our knowledge, this is a novel impurity and not reported elsewhere.
Butyrates ; analysis ; isolation & purification ; Drug Contamination ; Lisinopril ; analysis ; Magnetic Resonance Spectroscopy ; Models, Molecular

In order to evaluate the hypotensive effect of the lisinopril, a long acting angiotensin converting enzyme inhibitor, 10 to 30mg of lisinopril were administered in 35 hypertensive Korean adults during six weeks after a week observation for washout with stepwise increments of the dose according to the response of the patients blood pressure in every two weeks. The results were ; 1) The supine blood pressures were decreased from 163.7+/-16.6/99.8+/-9.3mmHg to 140.7+/-15.5/87.4+/-9.9mmHg at the end of six weeks' drug therapy(p<0.001). The standing blood pressures were also decreased conferrably and to the some lower levels. 2) In 14 patients to whom the drug was administered longer period(12 to 28 weeks) the blood pressure lowering effects were maintained at the level of that of 6th week. 3) Hematologic examination and blood chemistry revealed no discernible abnormal findings before and after the treatment. 4) In those patients who showed no adequate blood pressure control with other classes of antihypertensive drugs the lisinopril was effective in lowering their blood pressures by adding small doses. 5) During the period of the study a few probably drug-related symptoms developed but not troublesome except dry cough and dry mouth shich forced to stop administering the drug after completion of six weeks' period in one patients. From above results we concluded that lisnopril is effective and safe for the treatment of hypertension in Korean adults.
Adult ; Antihypertensive Agents ; Blood Pressure ; Chemistry ; Cough ; Humans ; Hypertension ; Lisinopril* ; Mouth ; Peptidyl-Dipeptidase A

BACKGROUND: The hypotensive effect of the lisinopril, a long acting angiotensin converting enzyme inhibitor, was studied. METHOD: 10mg of lisinopril was administered in 30 hypertensive Korean adults during twelve week after a weeks observation for washout with stepwise increments of the dose according to the patients blood pressure in every two weeks. RESULTS: The supine blood pressures were decreased from 173.3+/-27.9/105.7+/-19.4mmHg to 131.8+/-23.1mmHg/81.4+/-18.7mmHg at the end of twelve weeks durg therapy(P<0.05). The standing blood pressures were also decreased conferrably and to the some lower levels. Hematologic examination and blood chemistry revealed no discernible abnormal findings before and after the treatment. During the period of the study a few probably drug-related symptom such as dry cough and dry mouth developed but not troublesome enough to stop administering. CONCLUSION: Lisinopril 10mg once daily regimen is well tolerated and effective in the treatment of hypertensive patients.
Adult ; Blood Pressure ; Chemistry ; Cough ; Humans ; Hypertension ; Lisinopril* ; Mouth ; Peptidyl-Dipeptidase A

Two trace impurities in the bulk drug lisinopril were detected by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) with a simple and sensitive method suitable for HPLC/MSn analysis. The fragmentation behavior of lisinopril and the impurities was investigated, and two unknown impurities were elucidated as 2-(6-amino-1-(1-carboxyethylamino)-1-oxohexan-2-ylamino)-4-phenylbutanoic acid and 6-amino-2-(1-carboxy-3-phenylpro-pylamino)-hexanoic acid on the basis of the multi-stage mass spectrometry and exact mass evidence. The proposed structures of the two unknown impurities were further confirmed by nuclear magnetic resonance (NMR) experiments after preparative isolation.
Chromatography, High Pressure Liquid ; methods ; Drug Contamination ; Lisinopril ; analysis ; Magnetic Resonance Spectroscopy ; Spectrometry, Mass, Electrospray Ionization ; methods

Severe intraoperative hypotension has been reported in patients on angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists. We describe a patient on lisinopril who developed refractory intraoperative hypotension associated with increased serum tryptase level suggesting mast cell activation (allergic reaction). However, allergology workup ruled out an allergic etiology as well as mastocytosis, and hypotension recalcitrant to treatment was attributed to uninterrupted lisinopril therapy. Elevated serum tryptase was attributed to our patient's chronic renal insufficiency.
Anaphylaxis ; Angiotensin-Converting Enzyme Inhibitors ; Humans ; Hypotension ; Lisinopril ; Mast Cells ; Mastocytosis ; Receptors, Angiotensin ; Renal Insufficiency, Chronic ; Tryptases

Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.
Animals ; Body Weight ; Creatinine ; Diabetes Mellitus ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; Glucose ; Kidney ; Lipoproteins, HDL ; Lisinopril ; Rats* ; Streptozocin ; Triglycerides ; Urea ; Vascular Resistance

Angioedema is a disorder characterized by well-demarcated nonpitting edema involving the tongue, floor of the mouth, larynx, lips, and face. The incidence of angiotensin converting enzyme(ACE) inhibitor related angioedema has been reported to be about 0.1% to 0.2%, and the time of onset is usually during the first week of therapy. These ACE inhibitors include captopril, enalapril, and lisinopril. A 53-year old man with an 8 month history of hypertension previously controlled with atenolol, was presented to the dermatologic department with angioedema of the face and tongue. He had begun therapy with captopril one day before this episode. Even though he was treated with epinephrine and methylprednisolone sodium succinate, the edema gradually progressed and finally dyspnea developed. He was urgently intubated and treated with steroids and pheniramine maleate in the intensive care unit. The edema resolved after 24 hours.
Angioedema* ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Atenolol ; Captopril* ; Dyspnea ; Edema ; Enalapril ; Epinephrine ; Humans ; Hypertension ; Incidence ; Intensive Care Units ; Larynx ; Lip ; Lisinopril ; Methylprednisolone Hemisuccinate ; Middle Aged ; Mouth ; Pheniramine ; Steroids ; Tongue

BACKGROUND: Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. METHODS: Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. RESULTS: Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-beta1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. CONCLUSION: Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.
Aldosterone ; Animals ; Collagen Type IV ; Connective Tissue Growth Factor ; Diabetic Nephropathies ; Fibronectins ; Lisinopril ; Mineralocorticoid Receptor Antagonists ; Peptidyl-Dipeptidase A ; Plasminogen Activators ; Rats ; Rats, Inbred OLETF ; Receptors, Mineralocorticoid ; Renin-Angiotensin System ; RNA, Messenger ; Spironolactone

The aim of the present study, performed on two different groups of volunteers, is to characterize the pharmacokinetics of lisinopril/hydrochlorothiazide combined tablet. After administration of high, medium and low doses of lisinopril/hydrochlorothiazide combined tablets, AUC and C(max) of two compounds both increase significantly with increase of dose. Neither normalized AUC/Dose nor C(max)/Dose has significant difference between every two tested dose groups. The similar results can be observed as for the parameters of t(max). Lisinopril and hydrochlorothiazide are both eliminated with linear characteristics. After repeated administration of lisinopril/hydrochlorothiazide combined tablets, AUC, C(max) and C(min) of lisinopril in the steady state increase. AUC and C(min) increase significantly. As for hydrochlorothiazide, AUC, C(max), C(min), and t(max) also increase in steady state. AUC and C(min) increase significantly. Administered with the test medication, lisinopril has an fluctuation index (FI) value of 2.29 and reaches a relative steady concentration. But hydrochlorothiazide has an FI value of 4.09 with relatively large fluctuating concentrations.
Adult ; Antihypertensive Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Asian Continental Ancestry Group ; Biological Availability ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Drug Combinations ; Female ; Humans ; Hydrochlorothiazide ; administration & dosage ; blood ; pharmacokinetics ; Lisinopril ; administration & dosage ; blood ; pharmacokinetics ; Male ; Tablets ; Young Adult