[Dietary supplements--evaluation of patient inquiries at a drug information service]. / Nahrungsergänzungsmittel--Evaluation der Patientenanfragen an einen Arzneimittelberatungsdienst.

BACKGROUND: Dietary supplements are a product group of foods, which are meant to supplement the general nutrition with micronutrients and other substances. They are widely used in Germany. We evaluated the frequency of their use and of information requirements concerning dietary supplements in patients who contacted the independent drug information service at TU Dresden. PATIENTS AND METHODS: All inquiries from 2008 to 2010 were evaluated regarding information requirement about dietary supplements, the kind of products used and characteristics of patients using supplements. Sociodemographic characteristics, kind and number of drugs and dietary supplements as well as underlying diseases were recorded from the inquiring patients. RESULTS: 23.3 % of persons looking for advice used dietary supplements. The most frequently used product groups included vitamins and minerals (52.5 %) as well as plant extracts (14.0 %). Information requirements were especially high for plant extracts and for products containing glucosamine/chondroitin and lutein/zeaxanthin. Users of dietary supplements were exposed to a higher number of different products than non-users. CONCLUSIONS: Information requirements were primarily detected for products without clearly proven benefits or for supplements which are advertised to relieve certain diseases or symptoms although the product characteristics do not support such utilization. The frequency of use of dietary supplements among patients which already receive multiple medications substantiates the necessity to include dietary supplements in assessments of drug interactions and to scrutinize indications for supplement use.

Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials.

BACKGROUND: The comparative efficacy and tolerability of conventional and biologic treatments for moderate-to-severe plaque psoriasis are unknown. OBJECTIVES: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate-to-severe psoriasis by means of the Psoriasis Area and Severity Index (PASI). METHODS: We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with >or= 75% decrease in PASI (PASI-75) at primary efficacy measurement (week 8-16). PASI-75 response rates of double-blind placebo-controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events. RESULTS: Twenty-four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double-blind placebo-controlled trials were eligible for meta-analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72-81%]. Adalimumab (RD 64%, 95% CI 61-68%) was superior to ciclosporin (RD 33%, 95% CI 13-52%), efalizumab (RD 24%, 95% CI 19-30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40-48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25-35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32-64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters. CONCLUSIONS: The efficacy of systemic agents approved for moderate-to-severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI-75 response. Published evidence questions regulatory guidelines that recommend biologics as second-line therapy for moderate-to-severe plaque psoriasis.

Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol.

St John's wort (SJW) is known to induce cytochrome P450 (CYP) 3A4 and P-glycoprotein through pregnane X-receptor activation. Our study evaluated the effects of long-term SJW administration on oral and intravenous pharmacokinetics of the nonmetabolized in vivo probe of P-glycoprotein, talinolol, in relation to intestinal P-glycoprotein expression. In a controlled, randomized study (N=9), the pharmacokinetics of oral (50 mg) and intravenous talinolol (30 mg) was determined before and after 12 days SJW (900 mg daily, Jarsin 300). Duodenal biopsies were taken and MDR1 genotypes assessed. SJW reduced the oral talinolol bioavailability by 25% (P=0.049) compared with water control. A 93% increase in oral clearance (P=0.177) and a 31% reduction in area under the serum concentration time curve (AUC; P=0.030) were observed. Renal and nonrenal clearance (CLNR), elimination half-life, peak serum drug concentration (Cmax), and time to reach Cmax were not significantly altered. After intravenous talinolol, SJW affected only CLNR (35% increase compared with water, P=0.006). SJW increased MDR1 messenger ribonucleic acid (mRNA) as well as P-glycoprotein levels in the duodenal mucosa. Subjects with the combined MDR1 genotype comprising 1236C>T, 2677G>T/A, and 3435C>T polymorphisms had lower intestinal MDR1 mRNA levels and displayed an attenuated inductive response to SJW as assessed by talinolol disposition. Long-term SJW decreased talinolol AUC with a corresponding increase in intestinal MDR1 expression, suggesting that SJW has a major inductive effect on intestinal P-glycoprotein. Interestingly, the magnitude of induction appeared to be affected by MDR1 genotype.

The pharmacokinetics of zinc from zinc gluconate: a comparison with zinc oxide in healthy men.

OBJECTIVE: Zinc supplementation is beneficial in some clinical conditions such as age-related macula degeneration (AMD). It has been suggested that zinc absorption is influenced by the form in which zinc is ingested. Therefore, the pharmacokinetics of zinc gluconate (organic) were compared with those of zinc oxide (inorganic). METHODS: 12 healthy male subjects aged between 21 and 31 years (24 years median) orally received daily doses of 20 mg metal zinc as zinc gluconate and 17.4 mg metal zinc as zinc oxide under randomized crossover conditions for 14 days each with at least 14 days as a washout. Zinc plasma concentrations were measured by means of inductively coupled plasma-atomic emission spectroscopy. RESULTS: C(max) was found 18.3% (10.3 - 26.3%) higher following multiple-dose administration of zinc gluconate as compared to zinc oxide (mean; 0.95% confidence interval of the relative differences between both treatment conditions; p < 0.05). AUC(0-24h) was noted 8.1% (1.9 - 14.3%) higher after zinc was given as zinc gluconate when compared to zinc oxide (p < 0.05) whereas t(max) did not differ between both treatment conditions. CONCLUSIONS: Zinc absorption in humans could be improved by zinc complexation with gluconate.

The effects of St John's wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men.

AIMS: To compare the effects of multiple dosing with St John's wort (Hypericum perforatum) extract and amitriptyline on heart rate variability, cognitive function and quantitative EEG (qEEG) with placebo in healthy humans. METHODS: A randomized, double-blind, cross over study of 12 healthy male volunteers. Subjects orally received capsules with 255-285 mg St John's wort extract (900 micro g hypericin content), 25 mg amitriptyline and placebo three times daily for periods of 14 days each with at least 14 days between. The doses of amitriptyline and St John's wort extract are comparable with respect to their antidepressant activity. Compliance was confirmed by coadministration of 10 mg of riboflavin with each capsule and detection of urinary vitamin B2 on treatment day 11 with high performance liquid chromatography. Measurements of heart rate variability, psychometric tests and qEEG were performed before start of medication and repeatedly on the last treatment day. RESULTS: St John's wort extract did not affect heart rate variability (HRV) whereas amitripytline significantly decreased it: the difference in the percentage number of adjacent RR intervals> 50 ms (pNN50) was 8.6 (-2.6, 19.9; mean; 95% confidence interval) between St John's wort extract and placebo and -17.6 (-24.7, -10.4) between amitriptyline and placebo. Neither St John's wort extract nor amitriptyline had an influence on cognitive performance such as choice reaction, psychomotor coordination, short-term memory and responsiveness to distractive stimuli. Amitriptyline but not St John's wort extract decreased self rated activity (P < 0.05). Both drugs caused significant qEEG changes. St John's wort extract increased theta power density. Amitriptyline increased theta as well as fast alpha power density. CONCLUSIONS: Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.

Effect of high dose verapamil on restenosis after peripheral angioplasty.

OBJECTIVES: We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Restenosis is the major limitation of PTCA. Calcium antagonists have demonstrated some potential as inhibitors of this process. METHODS: A total of 98 patients with peripheral occlusive arterial disease (POAD), stable angina pectoris, mild hypertension and at least one additional risk factor increasing the likelihood of restenosis after angioplasty were selected for this placebo-controlled, double-blind, randomized trial. Verapamil (240 mg twice daily) or placebo was taken for 6 months. Efficacy variables assessed before and after angioplasty and at 6 weeks and 6 months after PTCA included thickness of the intima/media complex degree of stenosis, interventricular septal thickness, crurobrachial pressure ratios of dorsalis pedis and posterior tibial arteries, distance to claudication and total vessel diameter. RESULTS: No significant intergroup differences emerged before or immediately after PTCA. Six weeks after angioplasty, a significant thickening of the intima/media complex in the treated vascular segment of 14.3% occurred in the placebo group versus 0% among verapamil patients (p < 0.01). At 6 months, the intima/media thickness was 35.7% greater in the placebo group but had decreased by 14.3% in the verapamil group (p < 0.001). At 6 months, a marked reduction in septal thickness was observed in the verapamil group versus that in the placebo group (p < 0.001). The rate of restenosis was also significantly lower in the verapamil group (p < 0.001). Few minor side effects were reported. CONCLUSIONS: In patients with POAD at increased risk for restenosis, the administration of high dose verapamil prevented recurrent stenosis for 6 months after successful peripheral angioplasty and was well tolerated.

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.

Ranitidine increases the bioavailability of nitrendipine in patients with arterial hypertension.

1. In a randomized placebo-controlled study, 12 hypertensive patients were treated po for one week with 20 mg nitrendipine once daily plus placebo, twice daily and later with the same dose of nitrendipine plus 300 mg ranitidine (150 mg twice a day). 2. When ranitidine was coadministered, plasma nitrendipine levels (0-24 h) were significantly increased (P < 0.001), although no significant increase in peak plasma nitrendipine level (Cmax) was observed due to the wide range of variation of this parameter (Cmax) in hypertensive patients. 3. Ranitidine coadministration increased the area under the curve for 24-h (AUC0-24) plasma concentration vs time, from 49.07 +/- 6.28 micrograms.h/l to 82.35 +/- 2.57 micrograms.h/l (P < 0.01). This significant increase caused a reduction in total body clearance from 2008.33 +/- 246.33 to 1284.00 +/- 182.16 ml/min (P < 0.002). 4. Nitrendipine bioavailability was increased by 89% when ranitidine was coadministered but the kinetic effect of this drug interaction is unlikely to be of clinical relevance since no adverse effects were observed in patients evaluated after ranitidine association.

[Effect of acoustic stress on immunoregulatory cells in female patients with systemic lupus erythematodes (SLE), patients with sarcoidosis and normal comparative subjects]. / Einfluss von akustischem Stress auf immunregulatorische Zellen bei Patientinnen mit systemischem Lupus erythematodes (SLE), Patienten mit Sarkoidose und gesunden Vergleichspersonen.

14 patients with systemic lupus erythematosus (SLE), 12 with sarcoidosis and two age- and sex-matched groups of healthy subjects were exposed to a 10-minute acoustic stress test. Healthy subjects and patients with sarcoidosis showed significant increases in leukocyte and lymphocyte counts (p less than 0.01), relative elevations of B and Tsc lymphocytes (p less than 0.01) and a relative reduction of Th lymphocytes (p less than 0.01). Patients with SLE showed the same characteristic alterations (p less than 0.01) but the degree of this cell mobilization was significantly less pronounced as compared with the healthy subjects (p less than 0.01). No dependence was found between corticosteroid therapy or disease activity and the cellular reaction in SLE patients. In SLE patients there thus seemed to be an attenuated immune response due to stress which may play an etiopathogenetic role in this disease.

Influence of nisoldipine on haemodynamic effects and plasma levels of digoxin.

In a placebo controlled double-blind study including 10 patients with heart failure the nisoldipine/digoxin interaction was studied. Nisoldipine was shown to elevate digoxin plasma concentrations significantly by about 15% (trough levels). During chronic combination therapy with nisoldipine trough levels and plasma concentrations 4 h after the morning dose of digoxin were 1.35 +/- 0.14 and 1.92 +/- 0.16 ng ml-1 respectively, whereas they averaged to 1.16 +/- 0.14 and 1.52 +/- 0.16 ng ml-1 with digoxin and placebo (P less than 0.05; mean +/- s.e. mean). Systolic time intervals were significantly altered by nisoldipine co-administration compared with digoxin plus placebo. In certain patients the elevation of digoxin plasma levels due to nisoldipine co-administration could be of clinical relevance.

[Effect of cimetidine and ranitidine on the pharmacokinetics and anti-hypertensive effect of nifedipine]. / Einfluss von Cimetidin und Ranitidin auf Pharmakokinetik und antihypertensiven Effekt von Nifedipin.

Simultaneous administration of cimetidine and nifedipine to six healthy volunteers produced an about 80% rise in maximal plasma levels and the area under the plasma level-time curve of nifedipine compared with results on nifedipine administration alone (P less than 0.05). After treatment for one week with 4 X 10 mg nifedipine daily and 3 X 200 mg cimetidine daily and 400 mg at night plasma level peaks of nifedipine averaged 87.7 +/- 19.1 ng/ml, while after 4 X 10 mg nifedipine alone they were only 46.1 +/- 10.6 ng/ml. Ranitidine produced an approximately 25%, nonsignificant, rise in plasma level-time curve and peak plasma levels of nifedipine. Seven hypertensives (WHO stage I and II) had a mean arterial blood pressure level of 127 +/- 2.5 mm Hg after two-week placebo administration, and of 109 +/- 2.38 mm Hg after four weeks of nifedipine alone at 4 X 10 mg daily (P less than 0.01). After additional administration of 1 g cimetidine daily for two weeks the mean blood pressure fell significantly to 95 +/- 3.1 mm Hg (P = 0.02), while blood pressure fell to 103 +/- 3.88 mm Hg after two weeks of additional administration of 300 mg ranitidine daily, a fall which was not significant (P greater than 0.05). The interaction of nifedipine and cimetidine is thus of clinical significance because of its pharmacodynamic effect.