Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to verify long-term therapeutic efficacy and tolerance of dihydroergocristine (DHEC, CAS 17479-19-5) in a double blind placebo controlled study, in elderly patients with psychosyndrome characterized by memory and behaviour impairment. Two hundred patients, aged more than 65 years, were randomly divided into two groups of one hundred each. The first group received one 6-mg DHEC tablet daily for four months and the other group received placebo. The evaluation parameter for efficacy was the neuropsychological test SCAG (Scale of Clinical Assessment for Geriatrics), administered before and after 30, 60 and 120 days. The results showed a significant difference between DHEC and placebo with regard to total and partial scores of SCAG as well as to single items (mental alertness, recent memory, disorientation, anxiety, mood depression, emotional lability, motivation, uncooperativeness, fatigue, headache, tinnitus). After as few as thirty days of DHEC treatment the severity of mental and psychological symptoms was markedly decreased (p vs placebo < 0.01), as documented by significant positive changes of SCAG items. The four-month double blind period was followed by a two-month single blind period, during which patients of both groups received placebo. At the end of these two months, SCAG total score was unfavourably increased in patients previously administered DHEC, although scores were still significantly lower both versus baseline and versus previous placebo patients. Safety was good (placebo: one case of diarrhea; DHEC: one case of gastralgia and dizziness). Nine patients dropped out for reasons unrelated to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Controlled study of the effect of dihydroergocristine on organic brain psychosyndrome]. 149 63

Aim of the study was to assess the activity of dihydroergocristine (DHEC, CAS 17479-19-5) in aged patients with impaired cognitive function. Twenty-five university hospital centres and 250 physicians participated in the study. 2,600 patients (1,104 males and 1,496 females, age range 50-80 years) were admitted to the study. Each patient was administered 6 mg/d DHEC for 120 days. Clinical evaluation was made through the SCAG Rating Scale registered at basal time, after 60 and 120 days. Responsivity to treatment was considered high when the final score was reduced by 30% and none if less than 10%. Analysis of results demonstrated that at the end of the study responsivity was high in 73% of cases, moderate in 20.4% and absent in 6.5%. Tolerability was very good as side effects were reported only in 3.16% of patients. Most frequent side effects were: nausea (1.23%), gastralgia (1.11%), headache (0.29%), hypotension (0.12%), vertigo (0.12%) and rash (0.08%). Drop-outs for gastralgia were reported only in 0.53% of the patients.
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PMID:[Epidemiologic study on the effectiveness and safety of dihydroergocristine in impaired memory and behavioral functions in aged humans]. 149 66

Levcromakalim (BRL 38227, CAS 94535-50-9) is a new antihypertensive drug with vasodilator activity due to activation of potassium channels in vascular smooth muscle. In this study, we treated 14 patients with essential hypertension on an out-patient basis to investigate the antihypertensive effect of levcromakalim by 24-h blood pressure monitoring for a 12-weeks treatment period. Levcromakalim significantly lowered blood pressure for 24 h without affecting standard deviation, range of variation and pulse rate. When 24-h monitoring period was divided into daytime (6:00-22:00) and nighttime (22:30-5:30), there were no statistically significant differences in magnitude of fall in blood pressure at night between baseline and end of treatment values. Four patients (28.5%) reported 6 adverse events, including headache, facial hot flushes, oedema and floating feeling. All symptoms were mild or moderate. These data show that levcromakalim controls ambulatory blood pressure both in the daytime and nighttime without changing the circadian rhythm of blood pressure, and suggest that levcromakalim will be an efficacious and safe antihypertensive drug.
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PMID:Antihypertensive effect of levcromakalim in patients with essential hypertension. Study by 24-h ambulatory blood pressure monitoring. 757 47

The chemically stable prostacyclin derivative iloprost (CAS 73873-87-7) infused intravenously induces vasodilation and inhibits platelet aggregation. Numerous clinical studies have shown that iloprost is beneficial in the treatment of obliterative arterial disease. As a topical therapy would have considerable advantages, the pharmacological activity and the tolerance of the drug was evaluated in several studies which included 73 healthy volunteers. The drug was tested in different galenical formulations: aqueous solution, various hydrogels and a fatty ointment. They were applied to intact as well as experimentally damaged (stripped) skin. The pharmacodynamic effects were determined by visual assessment, colorimetry and laser Doppler velocimetry. Moreover, the volunteers were monitored for systemic side effects including changes in blood and urine. After the solution was applied under occlusion, iloprost induced erythema at dose levels of at least 50/25 ng/cm2 (intact/stripped skin). Applied to intact skin, erythema lasted for up to 5 days. When the drug was applied to stripped skin the effect was shorter (24 h). Following low doses, erythema was confined predominantly to the follicles whereas homogeneous redness was induced by higher iloprost doses. Thus penetration seems to occur in particular via the follicles with the horny layer acting as a penetration barrier and as a drug reservoir. High doses (400/150 ng/cm2) induced edema in all cases when applied to intact/stripped skin. When applied to large areas of the skin, increased iloprost serum levels (< or = 80 pg/ml) as well as systemic side effects (inhibition of platelet function, flush, headache) were observed. Tachyphylaxia did not develop after the application of 25 micrograms/100 cm2 once daily for 60 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological activity and local and systemic tolerance of topically applied iloprost. 768 25

The objective of this study was two-fold: 1. to determine the pharmacokinetic parameters and the bioavailability of two 20 mg isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) preparations (treatments A and B) after single oral administration and 2. to evaluate the absolute bioavailability of IS-5-MN, which was possible by the administration of a third IS-5-MN preparation (treatment C) by the intravenous route (1 mg/ml, dose 20 mg). The three preparations were examined in 24 healthy volunteers according to a randomized 3-way cross-over design, blood samples were withdrawn up to 24 h following the administration of IS-5-MN and plasma concentrations of IS-5-MN were quantified by a gas chromatography method. The two oral preparations led to peak concentration values of about 360 ng/ml of IS-5-MN in the mean 0.90 h (treatment A) and 0.97 h (treatment B) after drug administration. The corresponding values for the infusion were 339.6 ng/ml and 2.59 h in the mean. For the areas under the curve (AUC(0-infinity)) mean values of 2733 (treatment A). 2724 (treatment B) and 2877 h x ng/ml (treatment C) were found. The absolute bioavailability of both oral treatments revealed values of 95.00% and 94.74% for treatments A and B, respectively. The statistical comparison (ANOVA, confidence intervals) of the pharmacokinetic parameters showed bioequivalence between both oral preparations and equivalence in the amount of drug absorption between both oral formulations and the i.v.-infusion. The observed undesired side effects (e.g. headache or nausea) are well known to occur after IS-5-MN administration.
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PMID:Evaluation of the pharmacokinetics and absolute bioavailability of three isosorbide-5-mononitrate preparations in healthy volunteers. 771 Apr 35

Acetylsalicylic acid (ASA, CAS 50-78-2) and ibuprofen (IB) are commonly used over-the-counter drugs for short-term treatment of pain of different origin. Ibuprofen lysinate (IBL, CAS 57469-76-8) is a water soluble form of ibuprofen for rapid absorption. This single blind, randomized, controlled study compared the incidence and severity of irritation of gastric and duodenal mucosa in normal healthy subjects (n = 45) following administration of IBL (Dolormin) 800 mg/d, ASA 2000 mg/d or placebo for 3 consecutive days. Gastric and duodenal mucosal injury were assessed endoscopically using a severity scale of 0-4 for mucosal erosions and mucosal hemorrhages. Mean gastric hemorrhage and erosion scores for ASA and IBL were significantly higher than those for placebo. In addition, ASA was found to be significantly more irritating to gastric mucosa than IBL, in both the incidence and severity of gastric erosions. No duodenal hemorrhages were detected in this study. The incidence of duodenal erosions was significantly higher in the ASA group (64%) than in both the IBL (6%) and placebo groups (0%) which were not significantly different. Only one subject (in the placebo group) reported an adverse experience (mild headache) during the study. The data suggest that both active treatments are more injurious to the gastric mucosa than placebo when given for 3 days to normal healthy volunteers, but that IBL 800 mg/d is significantly less injurious to the gastric and duodenal mucosa than ASA 2000 mg/d.
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PMID:Effects of ibuprofen lysinate and acetylsalicylic acid on gastric and duodenal mucosa. Randomized single-blind placebo-controlled endoscopic study in healthy volunteers. 794 19

A pharmacokinetic-pharmacodynamic cross-over study in a group of volunteers (8 male, 4 female) was performed to evaluate the activity and plasma levels of a new sustained-release metoclopramide (CAS 364-62-5) formulation (Cronoprimperan) in comparison to a standard formulation (Primperan). During the course of this trial volunteers on both medications complained of mild to moderate adverse effects as headaches and drowsiness. Elevated monocyte counts were seen in all volunteers at the end of the study without determinable relationship to the medications. No relevant differences were observed between the two preparations in the standard motor and coordination tests. The new sustained-release metoclopramide formulation showed 12-h coverage with a plateau shaped form for achieving constant blood levels throughout the day without reaching blood concentrations above clinically tolerable limits.
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PMID:Study of pharmacokinetics and pharmacodynamics of two preparations of metoclopramide. 801 Oct 7

The pharmacokinetic and pharmacodynamic effects of co-administration of flosequinan (BTS 49465, CAS 76568-02-0) and digoxin (CAS 20830-75-5) were investigated in 12 healthy volunteers. A 4-day, open, lead-in phase established the pharmacokinetics of flosequinan (100 mg on the first day and 50 mg for the next 3 days) and was followed by a 24-day open interaction phase. Digoxin was administered alone (0.75 mg for the first 3 days and 0.5 mg for the next 4 days) to establish steady-state pharmacokinetics and in combination with flosequinan (100 mg on the 8th day and 50 mg for the next 14 days with 0.5 mg digoxin daily), and finally digoxin alone (0.5 mg for the remaining 3 days). No statistically significant differences were observed for any of the pharmacokinetic parameters for flosequinan, its major metabolite BTS 53554, or digoxin when flosequinan and digoxin were administered alone or concomitantly, but the confidence intervals for differences were relatively wide. Overall diastolic blood pressure was significantly lowered by 10% with concomitant treatment compared with flosequinan monotherapy. There were no significant effects on overall heart rate or systolic blood pressure, although pre-dose heart rate was increased by 6% during concomitant administration compared with digoxin alone, and remained high and digoxin alone. Adverse events (headache, nausea and vomiting) were reported by 2 volunteers on digoxin and 5 on concomitant therapy. One volunteer was withdrawn during concomitant therapy because of severe headache and vomiting. The results from this study indicate that no pharmacokinetic interaction occurred during concomitant administration of flosequinan and digoxin in healthy volunteers.
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PMID:Effects of concurrent administration of flosequinan and digoxin on the pharmacokinetics of each drug. 819 94

In this multicenter, placebo-controlled study, 16 patients with mild to moderate essential hypertension were treated with 10 mg/day isradipine retard (PN 200-110, Lomir SRO, CAS 75695-93-1) for 3 weeks. The study started with a 2 week placebo wash out phase. 13 patients were randomised to an exclusive placebo therapy. After the placebo wash out phase, following the 1st medication in active therapy and after the end of therapy, 24-h blood pressure profiles were recorded. The profile under placebo on the 1st medication was separated by a one-week intervening placebo therapy for all patients. On active therapy, the systolic as well as the diastolic blood pressure (day time, night time and 24-h mean values) were significantly reduced. The antihypertensive effect of the active therapy became already manifest after the 1st medication and was augmented after 3 weeks of therapy. In the placebo group no parameter of the 24-h profiles changed significantly. The tolerability of treatment was excellent in 14 (87.5%) of the isradipine patients and in 10 (76.9%) of the placebo group. In one of 16 patients in the active group, adverse events (flush and ankle oedema) were observed. However, therapy could be continued. In one patient of the placebo group, oedema of the fingers was noticed, in another headache was documented. In the placebo group two patients discontinued the study due to inefficacy, in the isradipine group one patient for the same reason; a second patient was excluded from this group due to a concomitant disease unrelated to the study drug.
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PMID:[Circadian antihypertensive effect of sustained-release isradipine in patients with essential hypertension in comparison to placebo]. 824 Apr 58

The linearity of the relationship between dose and plasma concentration of nifedipine has been investigated in healthy male and female subjects under steady state conditions following application of a fatty alcohol matrix slow release nifedipine (Aprical long, CAS 21829-25-4) formulation at a dose rate of 60, 90 and 120 mg once daily. Plasma concentrations showed a broad plateau associated with mean residence times exceeding 20 h. On Day 4 mean pre-dose nifedipine concentrations were 20.5, 24.9, 31.8 ng/ml and Cmax values were 42.3, 51.7 and 93.9 ng/ml for the 60, 90 and 120 mg dose, respectively (n = 15). After dose normalisation there was no significant difference (Wilcoxon matched pair test) in the mean AUCs. Adverse reactions, mainly headache and flushes, were observed at all dose levels but the frequency was not dose-dependent. In view of the demonstrated proportionality between dose and AUC and the long duration of the plateau plasma concentrations it is concluded that this slow release formulation is suitable for once daily administration at dose rates up to 120 mg daily.
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PMID:Steady state kinetics of a fatty alcohol-based slow-release nifedipine for once a day application. 836 4


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