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Biomedical subjects

M S Laher

Publications and source records attributed to M S Laher.

At least 19 recordsLinked to original sources
PubMed1996

Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function.

An open, randomised, cross-over study was performed to investigate the pharmacokinetics of enalaprilat, administered as 20 mg enalapril both as monotherapy and in combination with hydrochlorothiazide (HCTZ 12.5 mg). Three groups of 6 hypertensive patients were enrolled [untreated diastolic blood pressure (DBP) 90-115 mm Hg]; normal renal function [glomerular filtration rate (GFR) > 81 ml min-1 1.73 m-2], mild renal impairment (GFR 51-80 ml min-1 1.73 m-2), and moderate renal impairment (GFR 31-50 ml min-1 1.73 m-2). The pharmacokinetics of enalaprilat and enalaprilat plus HCTZ correlated predictably with renal impairment with increased plasma concentrations and decreased urinary elimination at lower values of GFR. The coadministration of HCTZ had no significant effect on the pharmacokinetics of enalaprilat in any group. We conclude that although the pharmacokinetics of both enalaprilat and HCTZ are related to renal function, HCTZ has no significant effect on the pharmacokinetics of enalaprilat and that dosage adjustment for both regimens should be based on renal function.

Adult↗
PubMed1994

Double-blind comparison of amlodipine and nifedipine retard in the treatment of mild to moderate hypertension.

The efficacy and safety profiles of amlodipine (5-10 mg once daily) and nifedipine retard (20-40 mg twice daily) were compared in 111 hypertensive patients (sitting DBP in 95-115 mmHg) during eight weeks of treatment in a randomised double-blind parallel group study. BP was measured 22-24 hours after the daily dose of amlodipine and 10-12 hours after a dose of nifedipine retard. Baseline sitting BPs of 175/105 mmHg and 168/104 mmHg were significantly reduced (P < 0.05) to 157/93 mmHg and 151/92 mmHg at the end of treatment in response to mean daily doses of amlodipine 7.3 mg and nifedipine retard 58.9 mg. There were no clinically significant changes in heart rate with either treatment. Three patients in the amlodipine group and five patients in the nifedipine retard group could not be considered in analysis. The total numbers of adverse events (considered related or possibly related to treatment) (42 vs. 36) as well as the numbers of patients experiencing such events (22 vs. 22) were similar in the amlodipine and nifedipine retard treated groups, respectively, but with a greater incidence of headaches in response to nifedipine retard and of oedema in response to amlodipine. Five patients in each treatment group discontinued therapy due to such events. Overall the results showed once daily amlodipine as equivalent to twice daily nifedipine retard in the management of mild to moderate hypertension.

Adult↗
PubMed1993

European experience with artex: the Tertatolol International Multicentre Study (TIMS).

The Tertatolol International Multicentre Study (TIMS) was aimed at assessing the efficacy and acceptability of 5 mg tertatolol (T) once daily over a 1-year period. The study was carried out in 230 patients (96 men, 134 women, mean age 51.5 +/- 0.7 years) with uncomplicated mild-to-moderate hypertension. After a 1-month placebo run-in period followed by a 1-month double blind placebo-controlled period, 213 patients entered and 166 completed the 1-year open period. A diuretic (D) was added if blood pressure (BP) was inadequately controlled with tertatolol alone. After 1 year, 88.5% of patients were controlled (sitting diastolic BP < or = 90 mmHg): 56.3% on single therapy (T) and 32.2% on dual therapy (T+D), respectively. After a 1-month double-blind period, the incidence of emergent symptoms was not significantly different between the placebo group and the tertatolol group. This low incidence was also observed over the 1-year period, side effects leading to the discontinuation of the treatment in 9.1% of the cases. In patients whose creatinine level was initially higher than 100 mumol/l, tertatolol significantly decreased creatinine level in the single but not in the dual therapy group. This study confirms that tertatolol is an efficient and well-tolerated antihypertensive drug, which improves renal function.

Adrenergic beta-Antagonists↗
PubMed1991

A retrospective study of myocardial infarction occurring in elderly patients in a coronary care unit.

Myocardial infarction is a major cause of morbidity and mortality particularly in the elderly. Coronary Care Unit monitoring has resulted in the improvement in prognosis in all age groups. In this study, the clinical course and outcome of 204 consecutive patients with acute myocardial infarction aged over 65 years is retrospectively analysed. All patients were managed in a Coronary Care Unit operating a needs related policy. Those under 75 years (120 patients) were compared to those over that age (84 patients). The groups differed in terms of clinical presentation, cardiac enzymatic rise and response to drug therapy. However they had similar complication rates, morbidity and mortality.

Age Factors↗
PubMed1991

The effects of age and renal impairment on the pharmacokinetics of co-administered lisinopril and hydrochlorothiazide.

The pharmacokinetics of combined lisinopril and hydrochlorothiazide have been studied following single and multiple oral doses to 'young' (reference), elderly and renally impaired hypertensive patients. Tablets containing the fixed combination of lisinopril 20 mg and hydrochlorothiazide 12.5 mg were administered as a single dose followed by daily administration for 6-8 days. Serum concentration and haemodynamic measurements were made at intervals up to 48 hours after the first and last doses. The serum profiles of both drugs were comparable with observations from previous studies, showing higher concentrations in the elderly and in the renally impaired patients. Similar differences have been reported for such patient groups when the drugs were administered separately, indicating an absence of pharmacokinetic interaction. Both drugs accumulated by about 30% on multiple daily dosing. There were no differences between the patient groups in the extent of accumulation. The combination of lisinopril and hydrochlorothiazide produced the expected hypotensive response, minimum BP values being recorded 4 and 6 hours after treatment. The higher concentrations in the elderly and renally impaired patients were not associated with a greater reduction in BP. The pharmacokinetic behaviour of lisinopril and hydrochlorothiazide given together to elderly and renally impaired hypertensive patients suggests that a fixed dose combination is appropriate and that no changes to the dosage regimen additional to those used for the individual agents are necessary.

Adult↗
PubMed1990

Pharmacokinetics of oral acetyl-L-carnitine in renal impairment.

Acetyl-L-carnitine 1.5 g and 3.0 g was administered as three divided doses on each of two occasions to 24 people with varying renal failure (creatinine clearance 127-8 ml.min-1). Plasma and urinary concentrations of total-L-carnitine, free (non-esterified) carnitine, short-chain esters and acetyl-L-carnitine were measured. The baseline (pre-study) concentrations of all four substances were related to renal function. Patients whose creatinine clearance was below about 30-40 ml.min-1 were had the highest concentrations. Renal elimination of all four substances was related to dose and to renal function. There was evidence for dose-related elimination, with greater elimination of the larger dose.

Acetylcarnitine↗
PubMed1990

ICI 141,292 (epanolol)--pharmacokinetics after single and repeated oral administration in the elderly with moderate renal impairment.

The pharmacokinetics of ICI 141,292 (epanolol) were studies over 3 days after a single oral 200 mg dose and then over 24 h after 12 consecutive daily oral 200 mg doses in 16 elderly subjects (aged 65 to 94 years) with moderate renal impairment (mean creatinine clearance 33.2 ml.min-1). There was wide inter-individual variability in peak plasma ICI 141,292 concentrations (Cmax) but no significant difference was found between mean Cmax after a single dose (44.3 ng.ml-1) and after 12 doses (37.4 ng.ml-1). The mean observed time to peak plasma ICI 141,292 concentration (tmax) after a single dose (1.61 h) did not differ significantly from that after 12 doses (1.75 h). On several occasions an analytically significant second peak in ICI 141,292 plasma concentration was observed. Following the peak(s), the plasma concentrations declined biphasically and a mean terminal phase plasma half-life (t1/2) of 28.3 (range 10.2-84.8) h was calculated after a single dose. The inter-individual variability in the area under the plasma concentration-time curve to 24 h AUC (0-24) was 54 fold but there was no significant difference between AUC (0-24) after a single dose (mean 226.0 ng.h.ml-1) and AUC (0-24) after 12 consecutive doses of ICI 141,292 (mean 232.4 ng.h.ml-1). The results show that consecutive daily administration of 12 oral doses of ICI 141,292 (200 mg) does not result in significant accumulation of drug in elderly subjects with moderate renal impairment.

Administration, Oral↗
PubMed1990

Lisinopril in elderly patients with hypertension. Long term effects on renal and metabolic function.

The efficacy and tolerability of lisinopril administered once daily were evaluated in a 12-week open study of 60 elderly patients aged between 65 and 85 years (mean 75 years) with essential hypertension. Mean sitting blood pressure was reduced from 190/106 +/- 6.3/1.3mm Hg (mean +/- SEM) at entry to 162/89 +/- 5.5/0.9 mm Hg after 12 weeks of treatment (p less than 0.001). There was no significant alteration in heart rate, and no occurrence of postural hypotension. The median daily dose of lisinopril was 20mg (range 5 to 40 mg) and only 4 patients required the addition of a diuretic. Mean glomerular filtration rate (GFR) at entry was 61.6 +/- 3.4 ml/min and was unchanged after 12 weeks of therapy. 25 patients continued to receive treatment for 1 year, and 20 of these completed 2 years of treatment. Control of blood pressure was maintained, and heart rate, biochemical parameters and GFR remained unaltered throughout the study. Renal function was preserved and renal blood flow, measured in a group of 14 patients, was significantly increased (p less than 0.025) at the end of the first year after treatment with lisinopril. Thus, in the elderly, lisinopril was well tolerated and highly effective in lowering blood pressure, and renal function was maintained.

Age Factors↗
PubMed1990

The pharmacokinetics of dilevalol in renal impairment.

Dilevalol, 200 mg, was administered orally as seven daily doses to three groups of six participants, with differing degrees of renal impairment. Values of Cmax, Tmax, half-life or renal elimination did not significantly change with decreased renal function. Values of area under the plasma concentration-time curves and pre-dose concentrations tended to increase with renal impairment and there was a significant, if small, correlation between these and glomerular filtration rate. The practical clinical consequences of these results is that impairment is not likely to be associated with significant accumulation of dilevalol.

Administration, Oral↗
PubMed1989

Cardioprotection and antihypertensive therapy. Are beta-blockers the only effective therapy?

Hypertension is a major risk factor for stroke and coronary heart disease and this increases with increasing age. It is a chronic disease which affects a quarter of the adult population. On its own or in conjunction with other risk factors, especially cigarette smoking, hypertension is associated with serious morbidity and high mortality. A large number of clinical trials have been undertaken to assess the efficacy of antihypertensive therapy in controlling high blood pressure and in reducing the morbidity and mortality associated with hypertension. These trials have studied more than 40,000 subjects worldwide as a result of which the benefits of treatment even in milder forms of hypertension are well established today. However, antihypertensive therapy has been disappointingly unsuccessful in the primary prevention of coronary artery disease despite the undoubted protection against malignant phase hypertension, heart failure, stroke and renal failure as demonstrated in the early Veterans Administration trial and subsequent studies. The success of post-infarction beta-blockade suggested that the wider use of beta-blockers prophylactically might limit hypertension-related coronary disease. Taking into account the adverse and metabolic effects of thiazide diuretics, beta-blockers together with calcium channel blockers must remain the drugs of choice as step one therapy in most patients with hypertension.

Adrenergic beta-Antagonists↗
PubMed1988

Lisinopril in the treatment of hypertensive patients with renal impairment.

Lisinopril, a long-acting angiotensin-converting enzyme inhibitor, is excreted unchanged by the kidney. To determine how reduced renal function affects the drug's antihypertensive efficacy and safety, we studied 26 patients with hypertension associated with impaired renal function, having glomerular filtration rates (GFRs) of 60 ml/minute or less. These patients were enrolled in an open trial of 12 weeks' duration. They were given single daily doses of lisinopril, starting with 2.5 mg in patients with a GFR of less than 30 ml/minute, and 5 mg in the other patients. The dose was titrated to a maximum of 40 mg daily according to the blood pressure response. A diuretic was then added if required. Mean sitting and standing blood pressures at four, eight, and 12 weeks of treatment were significantly reduced compared with pretreatment values. The median dose of lisinopril was 10 mg daily (range, 2.5 to 40 mg), and only four patients required the addition of a diuretic. The mean GFR was unchanged during the study (36 +/- 16.4 ml/minute at baseline, 39 +/- 20.8 ml/minute after 12 weeks of treatment). Twenty-five patients completed the study. The one patient withdrew because of nausea and vomiting due to reflux esophagitis, which was probably not drug-related. Another patient had transient angioneurotic edema and continued to receive lisinopril. No clinically significant hematologic or biochemical abnormalities were observed. Sixteen patients continued to receive lisinopril for one year. Blood pressure control and GFR were well maintained throughout. Thus, in a group of patients who are often difficult to treat, lisinopril provided highly effective blood pressure control and was generally well tolerated.

Adult↗
PubMed1988

Antihypertensive and renal effects of lisinopril in older patients with hypertension.

The antihypertensive efficacy and safety of lisinopril were assessed in 60 older patients with a mean age of 75 years (range, 65 to 85 years) in a 12-week open study. Mean ( +/- SEM) blood pressure while sitting was reduced from 190/106 +/- 3.3/1.8 mm Hg at entry to 162/89 +/- 3.2/1.6 mm Hg after 12 weeks of treatment (p less than 0.001). There was no significant alteration in heart rate, and postural hypotension did not occur. Mean glomerular filtration rate at entry was 61.6 +/- 3.4 ml/minute and was unchanged after 12 weeks of therapy at 62.2 +/- 3.0 ml/minute. Fourteen patients continued to receive lisinopril for a period of one year. Blood pressure remained controlled throughout and heart rate remained unchanged. There was a significant reduction in mean arterial pressure from 128.8 +/- 1.9 mm Hg to 105.1 +/- 1.5 mm Hg (p less than 0.001). Biochemical parameters remained unaltered. There was a significant increase in renal blood flow (p less than 0.025) and a corresponding reduction in renovascular resistance (p less than 0.001) following long-term therapy with lisinopril. Thus, lisinopril was generally well-tolerated and highly effective in lowering blood pressure in older hypertensive patients, whereas at the same time renal function was not adversely changed.

Aged↗
PubMed1988

Pharmacokinetics of amlodipine in renal impairment.

The pharmacokinetics of amlodipine was studied in 27 subjects with renal function ranging from normal to dialysis-dependent. Amlodipine (as a single 5-mg capsule) was administered once daily for 14 days and its plasma concentrations were measured by gas chromatography during and after treatment. Renal impairment had little or no effect on the pharmacokinetics of amlodipine. The elimination half-life was of the order of 50 h, similar to previously observed values, and did not vary with differences in renal function. Steady-state predose concentrations were observed after the ninth dose. Accumulation of amlodipine to steady-state levels was not significantly different from that expected on theoretical grounds and did not significantly change with renal function. These results suggest that once-daily administration of amlodipine is suitable for all degrees of renal function and that dosage adjustment is not necessary in renal impairment.

Adult↗
PubMed1987

Lisinopril in elderly patients with hypertension.

The antihypertensive efficacy and safety of lisinopril, a long-acting angiotensin-converting enzyme inhibitor, were assessed in 40 elderly patients (aged 65 years or over) with mild to moderate systolic/diastolic or isolated systolic hypertension, in an open study of 12 weeks' duration. Lisinopril was given orally in single daily doses. The starting dose was 5 mg in patients with glomerular filtration rate (GFR) of 30-60 ml/min and 10 mg in patients with GFR greater than 60 ml/min. The dose of lisinopril could be titrated upwards to a maximum of 40 mg daily according to blood pressure response. A thiazide diuretic was then added if blood pressure was not controlled. Thirty-six patients completed the study. Mean sitting blood pressure was significantly reduced by lisinopril treatment. There was no significant alteration in the heart rate, and postural hypotension did not occur. The median dose of lisinopril given was 20 mg daily (range 5-40 mg daily), and only two patients had a diuretic added to the lisinopril. One patient was withdrawn from the study because of unstable angina, and another was discontinued from lisinopril treatment because of anorexia and facial flushing. One patient was withdrawn after 8 weeks because of interruption of lisinopril therapy for a transurethral resection of the prostate, and one patient was lost to follow-up. No clinically significant haematological or biochemical changes were observed. The mean glomerular filtration rate was unchanged during the study. Proteinuria did not occur de novo, nor did established proteinuria increase. Thus lisinopril was well-tolerated and effective therapy in a group of elderly hypertensive patients.

Aged↗
PubMed1985

Captopril for refractory hypertension in patients with impaired renal function.

The use of captopril in 19 patients with renal parenchymal disease and refractory hypertension was studied for a mean period of 12 months. There was a significant reduction in the systolic and diastolic blood pressures, with a reduction in the mean arterial pressure of 29 mmHg. The mean maintenance dose of captopril was 142 mg daily in three divided doses. All but one of the patients required a diuretic for satisfactory blood pressure control and 3 patients were also given a beta-blocker. In all patients a simplification of the previous therapeutic regimen was achieved. A significant rise in serum creatinine was noted in 2 patients, one of whom had to be withdrawn from the study. Despite the presence of renal functional impairment, proteinuria did not occur de novo nor did established proteinuria increase. Leukopenia was noted in any of the patients in this group.

Blood Pressure↗
PubMed1985

Pharmacokinetics and bioavailability of pinacidil capsules in human volunteers.

Pinacidil is a new and potent vasodilator, which has recently been used in the treatment of various forms of hypertension. In this study pharmacokinetic parameters were determined following administration of intravenous (0.2 mg/kg) and capsule (12.5 mg) formulations of pinacidil to twelve healthy volunteers. The serum half-life (t1/2) and volume of distribution (Vd) of pinacidil were 2.04 +/- 0.40 h and 1.4 +/- 0.4 l/kg respectively, while the elimination rate constant (k el) was 0.34 +/- 0.07 h-1. The mean bioavailability of pinacidil (capsule formulation) was 57% +/- 16 S.D. Mild side-effects such as dizziness, headache and fatigue were noted in two volunteers following intravenous administration of pinacidil, while no side-effects were reported with the oral formulation.

Administration, Oral↗