Biomedical subjects

G Weidinger

Publications and source records attributed to G Weidinger.

At least 55 records · Page 3Linked to original sources

PubMed1997

Different concepts in first-line treatment of essential hypertension. Comparison of a low-dose reserpine-thiazide combination with nitrendipine monotherapy. German Reserpine in Hypertension Study Group.

Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment. We compared the efficacy and tolerability of the fixed combination of reserpine (0.1 mg) plus the thiazide clopamid (5 mg) with its single components and the calcium-antagonist nitrendipine (20 mg) in a randomized, double-blind, parallel study of 273 hypertensive patients with diastolic blood pressure (BP) between 100 and 114 mm Hg. The four groups did not differ regarding baseline characteristics (mean age, 58 years; 51% men; mean BP after a 2-week placebo period, 158 to 160/103 to 104 mm Hg). After 6 weeks of treatment with one capsule daily, mean reductions in sitting BP from baseline at 24 hours after dosing in the reserpine-clopamid combination, reserpine, clopamid, and nitrendipine groups were -23.0/-17.1, -14.0/-11.7, -13.6/-11.9, and -11.6/-12.3 mm Hg, respectively (2P < .01). The corresponding normalization rates (diastolic BP < 90 mm Hg) were 55%, 40%, 36%, and 33% (2P = .11). All patients whose BP had not been normalized at this point received two capsules of the respective medication once daily from weeks 7 to 12. At week 12, mean BP reductions were -25.7/-18.1, -14.6/-12.2, -17.7/-13.4, and -14.9/-15.3 mm Hg in the four groups, respectively (2P < .01). The respective normalization rates were 69%, 35%, 39%, and 45% (2P < .0001). Linear regression modeling indicated that reserpine and clopamid combined acted more than additively. As regards tolerability, adverse experiences were observed in 27%, 28%, 29%, and 48% of patients, respectively (2P < .05). The respective rates of premature discontinuation because of adverse effects were 3%, 3%, 7%, and 13% (2P = .06). In conclusion, a low-dose combination of reserpine and clopamid lowered BP significantly more than both the components alone and nitrendipine. Moreover, the combination was tolerated as well as its components and significantly better than nitrendipine. Thus, the use of this low-dose reserpine-thiazide combination appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.

Adolescent↗

PubMed1997

Low-dose (1.25 mg/kg) cyclosporin A: treatment of psoriasis and investigation of the influence on lipid profile.

This study was designed to investigate the therapeutical efficacy of a comparatively low dose cyclosporin A (1.25 mg/kg/day) in the treatment of psoriasis and to assess the influence of cyclosporin A on lipid profiles. In the first, double-blind part of the study, 133 patients with moderate to severe psoriasis were randomized to receive a daily dose of 1.25 or 2.5 mg cyclosporin A/kg or placebo for a period of 10 weeks (period I). Subsequently, the patients entered a second open-label 12-week study (period II), in which the dosage could be increased up to 5.0 mg/kg/day. This was followed by a period of 4 weeks without treatment. After 10 weeks the percentage improvement from baseline in the Psoriasis Area and Severity Index (PASI) was 5.9% on placebo, 27.2% on 1.25 mg/kg/day and 51.0% on 2.5 mg/kg/day cyclosporin A. The final average dose at the end of study period II was 2.99 mg cyclosporin A/kg/day. At this time the PASI was reduced by at least 75% in 63.0% of the patients. From this group of good responders no patient relapsed (PASI > 50% of baseline) during the four weeks after termination of active treatment. No significant effects of the drug on the lipid profiles were detected. We conclude that 1.25 mg cyclosporin A/kg/day is superior to placebo in the treatment of psoriasis vulgaris and that a dose reduction to 1.25 mg/kg/day should be considered in patients responding well to a conventional dose between 2.5 and 5.0 cyclosporin A/kg/day.

Adolescent↗

PubMed1997

Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor.

The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated. A total of 127 adult outpatients with diastolic blood pressure between 100 and 114 mmHg were randomized into this double-blind, parallel group study. After a 2-week wash-out period and a subsequent 2-week placebo run-in period, they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide (R/C), or 5 mg enalapril. If diastolic blood pressure was not normalized after 3 weeks of therapy (i.e. DBP < 90 mmHg), the dosage was doubled from week 4 to 6. The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure (DBP/SBP) after 3 weeks of therapy. Secondary variables included the change in DBP and SBP after 6 weeks of therapy, the BP normalization rates at 3 and 6 weeks and, concerning tolerability, the rates of adverse events after 6 weeks of therapy. An intent-to-treat analysis was performed. The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics (mean age 57 or 58 years, respectively; 63% or 56% males, respectively; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups). After 3 weeks of treatment with one capsule daily, mean SBP/DBP reduction from baseline (24 h after last medication intake) in the R/C combination group was -19.6/ -17.0 mmHg, in the enalapril group -6.1/ -9.5 mmHg (between-group comparison: 2p < 0.01 for both parameters). The normalization rates for DBP (< 90 mmHg) were 64.1% (R/C) and 28.6% (enalapril) (2p < 0.01). Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients (17.2%) in the R/C group and in 9 patients (14.3%) in the enalapril group (NS). Two patients in the enalapril group discontinued the study prematurely due to adverse events (cough; skin eruption). In the treatment of mild-to-moderate hypertension, a low-dose combination of reserpine and clopamide once a day is considerably more effective than, and as tolerable as, 5-10 mg of enalapril once a day. These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension. Besides, the "old" reserpine-diuretic regimen also in these days appears to be a rational alternative to "modern" monotherapies.

Adult↗

PubMed1997

Evaluation of 6 weeks treatment of terbinafine in tinea unguium in a double-blind trial comparing 6 and 12 weeks therapy. The Lagos V Study Group.

Terbinafine (Lamisil) has been registered throughout the world for the treatment of finger and toenail onychomycosis. The recommended duration of treatment of toenail onychomycosis based on phase III studies is 12 weeks. This study was designed to determine: (i) if patients in whom the proximal part of the toenails was not affected respond as well after 6 weeks treatment as after 12 weeks treatment; (ii) to identify factors which may allow selection of patients for shorter treatment duration; and (iii) confirm that 6 weeks therapy is sufficient in fingernail mycosis. One hundred and forty-eight patients received 250 mg terbinafine daily for either 6 or 12 weeks in a double-blinded manner, and were allowed until 48 weeks after start of therapy. Cure of the nail infection was defined as negative mycological tests (mycological cure) and progressive growth of normal nail (clinical cure). Mycological cure was recorded in 43 of 72 (59.7%) in the 6-week group and 55 of 76 (72.4%) in the 12-week group. In those who completed the study per protocol in the 6-week group, 34 of 61 (55.7%) were cured mycologically corresponding to 46 of 56 (82.1%) in the 12-week group. The overall clinical and mycological cure rates for the two groups were 28 of 61 (45.9%) and 33 of 56 (58.9%), respectively. In the small number of patients with associated fingernail infection, all were improved and six of eight (75.0%) were cured after a duration of treatment of 6 weeks. A priori risk factors for failure of cure could not be identified in either group. However, shorter duration of disease prior to treatment and no involvement of the big toenail was associated with a trend toward better responses in both groups. It can be concluded from this study that, in toenail mycosis without visible matrix involvement, 6 weeks treatment of terbinafine is generally not sufficient, whereas fingernail infections respond well to this short therapy.

Adult↗

PubMed1996

German randomized double-blind multicentre comparison of terbinafine and itraconazole for the treatment of toenail tinea infection.

One-hundred and ninety-five patients with toenail tinea unguium were recruited to a multicentre double-blind clinical trial. Patients were given 250 mg terbinafine or 200 mg itraconazole daily for 12 weeks, with follow-up for a further 40 weeks. At the end of the study, mycological cure rates were 81% (70/86 assessed) for terbinafine and 63% (53/84 assessed) for itraconazole (two-tailed, P < 0.01). The length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (two-tailed, P < 0.05). Patient self-assessment also favoured terbinafine, with 65% evaluating it as good to very good, compared with 58% for itraconazole. Before treatment the terbinafine group had a mean of 6.7 and the itraconazole group 6.3 affected nails per patient. Total cure was achieved in 69% of terbinafine and 61% of itraconazole affected nails. We conclude that terbinafine is more effective than itraconazole in the treatment of toenail tinea infection.

Adult↗

PubMed1996

Influence of isradipine and spirapril on left ventricular hypertrophy and resistance arteries.

Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Effects of bunazosin and atenolol on serum lipids and apolipoproteins in a randomised trial.

The effects of bunazosin and atenolol on serum lipids and lipoproteins after 6 months of treatment were compared in this multicentric, double-blind, randomised trial. A total of 174 patients with mild to moderate essential hypertension from 15 hospitals in Germany and Poland was included in the study. Eighty-seven were treated with the alpha-receptor blocker bunazosin and the same number with the beta-blocker atenolol. Systolic and diastolic blood pressure decreased significantly in both groups, whereas only atenolol decreased pulse rate. In the bunazosin group HDL-cholesterol was significantly increased after 6 months of treatment, whereas all other analysed parameters remained unchanged. In the atenolol group total cholesterol, LDL-cholesterol, total triglycerides, apolipoprotein E, VLDL-cholesterol and VLDL-triglycerides were significantly increased after 6 months of therapy. There was a significant difference between bunazosin and atenolol for total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, VLDL-triglycerides and apolipoprotein B levels. As a consequence, there was a significant difference in the atherogenic index of both groups. We conclude that bunazosin is favorable in the treatment of high blood pressure, because the coronary risk is not negatively influenced as shown for atenolol.

Adrenergic alpha-Antagonists↗

PubMed1996

Anti-inflammatory efficacy of low-dose cyclosporin A in psoriatic arthritis. A prospective multicentre study.

Fifty-five patients with psoriatic arthritis were treated with a low dose of cyclosporin A (CyA) (mean dose 2.7 mg/kg per day) for a period of 6 months to investigate the efficacy of CyA on disease parameters. Significant improvement in the joint complaints and inflammation parameters was observed including a decrease in the number of painful (-46%) and swollen (-45%) joints, tenderness (Ritchie Index: -50%) and degree of swelling (-46%), patient's assessment of pain (-35%), the duration of morning joint stiffness (-37%), as well as a decrease in C-reactive protein (-52%). A 50% reduction of joint complaints required a total of 24 weeks, whereas a 50% reduction of skin involvement was achieved after 5-6 weeks of treatment. Four patients left the study due to adverse events: creatinine level increase in two patients, hypertension in one patient and gastroenteritis in the fourth patient. Joint scintigraphy in 18 patients indicated an improvement or stable condition in 61% of cases after a mean follow-up of approximately 8 months. The results of this prospective study show that low-dose CyA effectively improves not only skin lesions, but also joint complaints in psoriatic arthritis.

Adult↗

PubMed1996

Antihypertensive efficacy and orthostatic tolerance of bunazosin vs nitrendipine: a multicentre double-blind randomized controlled study.

A multicentre double-blind randomized controlled study was conducted in 358 patients with mild to moderate essential hypertension. The goal was to compare the antihypertensive efficacy, tolerability, and in particular postural hypotension of the alpha 1-adrenoreceptor blocker bunazosin with the calcium channel blocker nitrendipine. Both treatment groups had comparable baseline blood pressure (BP) values, namely diastolic BP (DBP) of 103.8 +/- 5.6 mm Hg in the bunazosin group, and 103.4 +/- 6.0 mm Hg in the nitrendipine group, respectively. Baseline systolic BPs (SBP) were 149.7 +/- 14.4 mm Hg (bunazosin) and 149.2 +/- 14.3 mm Hg (nitrendipine). After 12 weeks of therapy, reduction of DBP (-6.1 +/- 11.7 mm Hg on bunazosin vs -6.9 +/- 9.9 mm Hg on nitrendipine; P = n.s.), and SBP (-4.4 +/- 14.3 mm Hg on bunazosin vs -7.0 +/- 14.4 mm Hg on nitrendipine; P = n.s.) was similar in both groups. During a provocative orthostatic tolerance test after the first dose, the incidence of prae-collapses (ie termination of the test due to orthostatic complaints) was higher on bunazosin (17 vs 2; P < 0.05) but orthostatic dysregulation symptoms (symptom score 1.37 on bunazosin vs 0.95 on nitrendipine; n.s.) and collapses (four on bunazosin vs one on nitrendipine; n.s.) occurred to a similar extent in both treatment groups. Three and 9 weeks after treatment, no increased susceptibility to orthostatic stress compared to baseline could be found in either group. Under daily life conditions, the frequency of orthostatic dysregulation was identical in both groups (0.8%). Bunazosin, however, was far better tolerated with 43.8% of the patients complaining of adverse events as opposed to 63.6% on nitrendipine (P < 0.001). The rate of early discontinuations due to adverse events was only 1.3% on bunazosin compared to 13.6% on nitrendipine (P < 0.001). In conclusion, bunazosin has a similar antihypertensive efficacy as nitrendipine. Despite an initially higher susceptibility to orthostatic stress under a provocative manoeuver, bunazosin evoked the same low incidence of orthostatic dysregulation symptoms as nitrendipine under daily life conditions, but was significantly better tolerated than nitrendipine.

Adrenergic alpha-Antagonists↗

PubMed1995

Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group.

OBJECTIVE: To compare the efficacy and tolerability of terbinafine and itraconazole in the treatment of toenail tinea unguium. DESIGN: Multicentre, double blind, parallel group study. SETTING: 17 university hospitals, one army hospital, and five dermatology practices. PATIENTS: 195 patients with clinically suspected toenail tinea and growth of dermatophytes in baseline culture; data on 86 patients in the terbinafine group and 84 patients in the itraconazole group were fully evaluated for efficacy. INTERVENTIONS: Daily dose of 250 mg terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40 weeks. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and clinical improvement (length and area of unaffected nail) at week 52 or at discontinuation of treatment. RESULTS: At the end of the study mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of 84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of 86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (2P < 0.05). CONCLUSION: Terbinafine is more effective than itraconazole in the treatment of toenail tinea infection.

Adult↗

PubMed1995

Improvement of myocardial perfusion by short-term fluvastatin therapy in coronary artery disease.

Patients with hypercholesterolemia have impaired coronary and peripheral endothelial function. In patients with coronary artery disease, intracoronary acetylcholine infusion or mental stress causes paradoxical vasoconstriction, whereas lowering cholesterol restores endothelial function. The impact of lipid lowering by fluvastatin on myocardial perfusion in hypercholesterolemic patients with perfusion abnormalities was assessed by thallium-201 single photon-emission computed tomography (SPECT). A total of 22 patients were treated with fluvastatin (40 mg once daily) for 6 weeks, followed by 40 mg twice daily if low density lipoprotein cholesterol (LDL-C) levels were decreased by < or = 30%. During the 12-week treatment period, myocardial perfusion was measured by quantitative SPECT after standardized stress testing at baseline and after 12 weeks. Preliminary results for 17 male patients (mean age, 59.3 +/- 6.7 years) are presented here. LDL-C decreased from 191 +/- 26 to 146 +/- 28 mg/dL (p < 0.001). In ischemic segments myocardial perfusion increased by 30% (280 +/- 100 to 365 +/- 110 counts per matrix; p < 0.001). In normal segments perfusion increased by only 5% (451 +/- 74 to 473 +/- 69 counts per matrix; p < 0.005). The change in perfusion rate between ischemic and normal segments was significant (p < 0.005). In conclusion, LDL-C lowering with short-term fluvastatin therapy improved myocardial perfusion, especially in areas of ischemia. This suggests that improvement is due to functional restoration of coronary endothelium by fluvastatin, before anatomic regression of stenosis can occur following long-term treatment.

Adult↗

PubMed1995

Treatment of toenail onychomycosis. A randomized, double-blind study with terbinafine and griseofulvin. LAGOS II Study Group.

BACKGROUND AND DESIGN: The fungicidal mode of action of terbinafine should make it feasible to reduce treatment duration in onychomycosis. For this reason, a randomized, double-blind study in 195 patients with severe dermatophyte infections of the toenails was performed comparing a 24-week treatment with terbinafine (250 mg/d) with a 48-week treatment with micronized griseofulvin (1000 mg/d). RESULTS: After 48 weeks, effective treatment was achieved in 67% of the patients treated with terbinafine and in 56% of those treated with griseofulvin (two-tailed P = .120). At a follow-up visit 24 weeks later, cure rates had decreased to 60% in the terbinafine group and to 39% in the griseofulvin group (two-tailed P = .006). At the same time, the mycological cure rate was 81% with terbinafine and 62% with griseofulvin (two-tailed P = .02). CONCLUSIONS: This study has demonstrated the longterm therapeutic superiority of terbinafine to high-dose griseofulvin in the treatment of toenail mycosis. Furthermore, with the new antifungal terbinafine, treatment is no longer necessary until all affected nail material has grown out.

Adult↗

PubMed1995

Short-duration treatment of fingernail dermatophytosis: a randomized, double-blind study with terbinafine and griseofulvin. LAGOS III Study Group.

BACKGROUND: Dermatophytic infections of the fingernail can be effectively treated with oral antifungal agents; however, a long duration of treatment, generally several months, is required for cure. OBJECTIVE: Our purpose was to compare the efficacies of short-duration treatment with terbinafine and griseofulvin in the management of fingernail dermatophytosis. METHODS: In this randomized, double-blind study 180 patients with fingernail dermatophytosis were treated with daily doses of either terbinafine, 250 mg/day, or microsized griseofulvin, 500 mg/day, for 12 weeks. Patients subsequently received placebo for 12 weeks and were observed for an additional 24 weeks. Drug efficacy was assessed by mycologic examination and measurement of the growth of unaffected nail. RESULTS: At the end of the study 76% of the group who received terbinafine and 39% of those who received griseofulvin were found to be completely cured (p = 0.001). Drug tolerability was equally good in both treatment groups, without any clinically relevant changes in laboratory biochemical values. CONCLUSION: Short-duration treatment (3 months) for fingernail dermatophytosis with terbinafine and griseofulvin is well tolerated. However, terbinafine was associated with a higher cure rate.

Adolescent↗

PubMed1995

Low-dose short-term cyclosporine versus etretinate in psoriasis: improvement of skin, nail, and joint involvement.

BACKGROUND: High-dose cyclosporine therapy significantly alleviates psoriasis within 2 to 4 weeks but is associated with a high rate of side effects. Reports are conflicting on the frequency and promptness of relapse after discontinuation of cyclosporine therapy. OBJECTIVE: Our purpose was to compare the efficacy and safety of low-dose cyclosporine with that of etretinate and the stability of remission after replacing cyclosporine therapy with topical anthralin during tapering of cyclosporine. METHODS: In a multicenter study 210 patients with moderate to severe chronic plaque-type psoriasis were randomly assigned to treatment with cyclosporine or etretinate. The initial dosages were 2.5 mg/kg/day for cyclosporine and 0.5 mg/kg/day for etretinate, which could be individually adjusted to 5.0 and 0.75 mg/kg/day, respectively. After a treatment phase of 10 weeks (phase 1) patients receiving cyclosporine were again randomly assigned to a group in which cyclosporine was replaced by topical dithranol (anthralin), or to another group in which the drug was tapered during the next 12 weeks (phase 2). All patients treated with etretinate discontinued therapy after 10 weeks and used topical dithranol. RESULTS: Mean Psoriasis Area and Severity Index decreased by 71% in the cyclosporine group and by 47% in the etretinate group during phase 1. After 10 weeks of treatment 47% of the patients treated with cyclosporine and 10% of those treated with etretinate showed a reduction of more than 80% in skin involvement. Sixty-four percent of the cyclosporine group and 48% of the etretinate group did not require an increase in the initial dosage, resulting in a mean daily dose of 3.0 and 0.53 mg/kg, respectively. There was significant alleviation of nail involvement and joint complaints in both groups. In phase 2 the increase in mean Psoriasis Area and Severity Index and the incidence of relapse were significantly higher in patients in whom cyclosporine was discontinued and replaced by dithranol than in patients in whom cyclosporine was tapered or who were pretreated with etretinate. During treatment four patients from the cyclosporine group and three patients of the etretinate group discontinued the study because of side effects. CONCLUSION: Low-dose short-term cyclosporine therapy for psoriasis is, in comparison with etretinate, highly effective and well tolerated. Individually adjusted cyclosporine therapy allows the majority of patients to continue the low dosage of 2.5 mg/kg/day and still achieve a good clinical response. Remission can be better preserved by tapering the drug than by discontinuing treatment abruptly.

Administration, Cutaneous↗

PubMed1995

Nail incorporation kinetics of terbinafine in onychomycosis patients.

Patients with toe-nail onychomycosis were treated with terbinafine (250 mg daily, n = 20) for either 6 or 12 weeks in a randomized double-blind study. Plasma and distal nail clippings were taken before initiation of therapy and 1, 6, 12, 18, 24, 36 and 48 weeks thereafter. Analytical data of terbinafine extracted from nail clippings or plasma were obtained by high-performance liquid chromatography (HPLC). Nail extracts and isolated HPLC terbinafine peaks were analysed using a combined gas chromatography-mass spectroscopy system (GC-MS) for unequivocal identification of the drug. Terbinafine could be detected in the distal nail in the majority of the patients within 1 week of starting therapy. Maximum terbinafine levels of 0.52 and 1.01 micrograms/g were measured after 18 weeks in the 6- and 12-week treatment groups, respectively. While plasma levels decreased rapidly after termination of therapy terbinafine was detected in the nails as long as 30 weeks (6 weeks treatment) and 36 weeks (12 weeks treatment) after termination of therapy at a range of 0.28-0.19 microgram/g. The drug concentrations measured at all time points are well above the minimum inhibitory concentration (MIC) for dermatophytes and other fungi. These data suggest that the drug reaches the nail plate rapidly and persists there for several months after cessation of active treatment.

Antifungal Agents↗

PubMed1995

Pharmacokinetic and pharmacodynamic properties and therapeutic use of bunazosin in hypertension. A review.

Bunazosin (CAS 52712-76-2), a quinazoline derivative, selectively blocks alpha1-receptors. In addition to its potent antihypertensive property, beneficial effects on lipid metabolism, glucose metabolism, vascular smooth muscle cell proliferation, it can be used in the presence of concomitant diseases, such as obstructive bronchitis, chronic renal insufficiency, peripheral arterial occlusive disease, and diabetes mellitus. In its extended-release formulation (bunazosin retard), it is generally a well-tolerated alpha1-blocker when compared to other agents in its class. Pharmacokinetic studies in normotensive volunteers showed that plasma peak concentration (Cmax) of bunazosin retard and bioavailability were approximately 50% and 81%, respectively, of the values of the standard non-retarded formulation. Bunazosin is metabolized mainly in the liver, and urine excretion accounts for only 10% of unchanged bunazosin. Following oral administration of 6 mg bunazosin retard to healthy volunteers, Cmax was 15 ng/ml, time to reach peak level (tmax) was 4 h and elimination half life was about 12 h. Bunazosin retard has Cmax and area underthe concentration curve (AUC) to be linearly related to the dose between 3 and 18 mg (r = 0.8). As expected, patients with impaired hepatic functions have shown an increase in AUC, Cmax, and elimination half live values. The hemodynamic effects of bunazosin are due to arterial vasodilation, reduced peripheral vascular resistance and cardiac afterload with moderate increase increase of cardiac output. Bunazosin was shown to decrease the systolic and diastolic blood pressure without a reflex tachycardia. In addition to its hypotensive effects bunazosin significantly increased the effective renal blood flow (by 34%) and creatinine clearance (by 37%) in patients with essential hypertension. In patients with impaired renal function bunazosin exhibits better increase in the effective renal plasma flow and glomerular filtration rate when compared to other alpha1-blockers (e.g. prazosin). Results of double-blind, randomized trials in 343 hypertensive patients showed bunazosin to be a equipotent hypertensive agent without multiple titration as usually necessary for other alpha-blockers. Diastolic blood pressure was normalized (< or equal 90 mmHg) or reduced by at least 10 mm Hg in 47% and 46% of patients, respectively. Results of two one-year long term studies in more than 600 ¿young¿ and ¿elderly¿ hypertensive patients gave no hint for tachyphylaxia. Bunazosin proved to be superior to prazosin in terms of orthostatic tolerance, as tested with the Schellong test. In conclusion due to its antihypertensive properties, beneficial effects on vascular smooth muscle cells, glucose metabolism , and lipid profile, and the less likelihood of orthostatic hypotension following treatment, bunazosin reard can be considered a useful antihypertensive agent.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1994

Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.

Adult↗

PubMed1994

Terbinafine in onychomycosis with involvement by non-dermatophytic fungi.

Sixty-five patients with onychomycosis involving the yeasts Candida albicans or C. parapsilosis, or the mould Scopulariopsis brevicaulis, were treated for up to 48 weeks with terbinafine 250 mg daily. At the end of therapy mycological and clinical cure rates were 70% and 54% for C. albicans, and 85% and 63% for C. parapsilosis, respectively. Three out of seven S. brevicaulis infections were cured. Within 6 months of therapy, relapses occurred in 45.5% of the cured patients in the case of C. albicans infections and in 12.5% of the cured patients in the case of C. parapsilosis infections. Treatment was generally well tolerated and, although adverse events occurred in 43% of the patients, they were responsible for cessation of therapy in only 8.6%. These results indicate that the use of terbinafine in onychomycosis is not restricted to dermatophyte infections.

Administration, Oral↗