Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 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

The effects of dimethindene maleate (CAS 3614-69-5) on the central nervous system-as sustained release pellets (Fenistil OAD; OAD = once a day) and sustained release tablets (Fenistil retard) with an immediate release fraction-were investigated by means of the oculodynamic test (ODT) and visual analogue scales and compared to loratadine (CAS 79794-75-5) and placebo. In the confirmatory part of the study 18 healthy volunteers were included in a single-blind, randomised, 3-way change-over design with Fenistil OAD, loratadine, and placebo. An additional, fourth exploratory arm with Fenistil retard was run in 6 (out of the 18) subjects after completing the main part of the study. The ODT includes electro-oculography, choice reaction task, and cardiologic parameters under workload. Visual analogue scales were used for subjective ratings on well-being and drug effects concerning wakefulness (sedation), excitation, dizziness, performance, effort, and dry mouth. The results show no relevant differences between either of the active drugs and placebo. Therefore it can be stated that after a single dose there is no sedating effect of dimethindene maleate compared to loratadine or placebo.
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PMID:Effects of dimethindene maleate on psychomotor performance in the oculodynamic test compared with placebo and loratadine. 887 38

Cefodizime (CAS 69739-16-8, HR 221) is a new third-generation cephalosporin with pharmacokinetic properties that make it suitable for once-daily administration in the treatment of lower respiratory tract infections (LRTI). Ninety-nine adult hospitalized patients (66 males, 33 females, median age 57.5 years) received a once-daily injection of 2 g cefodizime for LRTI. Median treatment duration was 8 days. Forty-two patients received cefodizime intravenously and 57 intramuscularly. Indications for treatment were as follows; primary lobar pneumonia (n = 36), bronchopneumonia (n = 14), secondary pneumonia (n = 3), aspiration pneumonia (n = 5), acute exacerbation of chronic bronchitis (n = 21), and of bronchiectasis (n = 9) and acute purulent bronchitis (n = 11). General condition was good in 29 patients and poor in 58; 12 patients were critically ill. The following pathogens were isolated at baseline (source: bronchial secretions, sputum or blood): S. pneumoniae (n = 47), Haemophilus spp. (n = 17), M. catarrhalis (n = 6), Streptococcus spp. (n = 9), Staphylococcus spp. (n = 5), Klebsiella spp. (n = 4), Pseudomonas spp. (n = 1), A. calcoaceticus (n = 1) and anaerobic organisms (n = 7). Fifty-nine patients were evaluable for bacteriological response and 82 for clinical response. Bacteriological outcome was satisfactory in 29/30 patients having LRTI with parenchymal involvement (97%) and in 29/29 patients without parenchymal involvement (100%). Clinical cure was achieved in 41/43 evaluable patients with parenchymal involvement (95%) and in 37/39 patients without parenchymal involvement (95%) in the per-protocol analysis and in 54/58 patients (93%) and 37/41 patients (93%), respectively, in the clinical intention-to-treat analysis. Three of the patients with an unsatisfactory clinical response died of infection during the study. Cefodizime was well tolerated. Adverse reactions--all of mild intensity--were tachycardia, lumbalgia and dizziness, each occurring in one patient. Cefodizime 2 g once daily either i.m. or i.v. was effective in the treatment of lower respiratory tract infections in hospitalized patients.
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PMID:Cefodizime once daily in the treatment of lower respiratory tract infections. 920 86

The present study was conducted to describe and compare the in vivo performance (systemic exposure), clinical and laboratory safety of a fixed combinational product of inhaled reproterol (CAS 54063-54-6) plus disodium cromoglycate (DSCG; CAS 15826-37-6) using a novel freon (CFC)-free metered dose inhaler (MDI), which uses 1,1,1,2,3,3,3-heptafluoropropane (HFA-227; CAS 431-89-0) as propellant and polyoxyethylene glyceryl trioleate (Tagat TO; CAS 68958-64-5) as surfactant relative to the conventional freon-driven MDI Allergospasmin in healthy male and female volunteers. Twenty-four young male and female healthy subjects were randomly allocated in gender-balanced fashion to 4 parallel treatment groups with single and repeated dosing of either reproterol + DSCG by HFA- or CFC-MDI (each time N = 8) or placebo by HFA- or CFC-MDI (each time N = 4) using matched placebo devices thus allowing a double-blind (with regard to placebo) approach. Treatments consisted of a single morning dose of 2 actuations followed 4 days later by a 1 week treatment course of 2 actuations four times daily. Subjects were investigated extensively in terms of blood pressure, pulse rate, electrocardiography, spirometry, respiratory rate, body temperature, laboratory safety (haematology, clinical chemistry, urinalysis) and clinical well-being. There were no treatment, compound or device related effects for any of the tolerability and safety end points. The treatments were well tolerated. In particular, there was no irritative cough or any sign of broncho-irritation on application. Adverse events were reported in a total of 9 subjects: 3/8, 4/8, 0/4 and 2/4 subjects treated with reproterol + DSCG by HFA-MDI, reproterol + DSCG by CFC-MDI, placebo by HFA-MDI and placebo by CFC-MDI, respectively. Of these, 6 events in 6 subjects receiving the active treatments were considered probably or definitely related to the test drug administration (i.e. adverse drug reactions): after reproterol + DSCG one subject in each treatment group (HFA-MDI and CFC-MDI) complained of an unpleasant bitter taste immediately after application; one further subject in each group complained of headache. Under treatment with reproterol + DSCG by CFC-MDI one male subject complained of mild transient nausea with onset on day 5. Under treatment with reproterol + DSCG by HFA-MDI one female subject complained of mild dizziness and mildly disturbed (blurred) vision with onset on day 1. All adverse events occurred only transitory and required no treatment. Systemic exposure, evaluated by the plasma concentrations of DSCG at 1 h after application, was slightly higher with the HFA-MDI compared to the CFC-MDI. It is concluded that the safety, tolerability and in vivo performance of the newly developed freon-free MDI is at least as well tolerable as the already marketed freon-driven conventional formulation.
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PMID:Tolerability and in vivo performance of a novel freon-free metered dose inhaler for a fixed combinational product of reproterol and disodium cromoglycate. 968 24

An oral solution available as ethanol-free droplets of the fixed drug combination tilidine-HCl 50 mg/naloxone-HCl 4 mg (CAS 27107-79-5 and CAS 465-65-6, respectively; Tilidin-ratiopharm plus Tropfen) was investigated in 12 healthy volunteers together with an ethanol-containing reference preparation for comparable bioavailability. The study was conducted in an open, randomized, two-way cross-over design applying single doses of 20 droplets (equivalent to 50 mg tilidine-HCl/4 mg naloxone-HCl) of either formulation in the fasting state. The drug plasma profiles were monitored for a period of 48 h by means of LC-MS/MS for tilidine and its active metabolite nortilidine, whereas GC-MS was employed in order to determine naloxone and its phase I metabolite, 6-beta-naloxole. Maximum concentrations (Cmax) achieved were 22.28 ng/ml (tilidine) and 92.78 ng/ml (nortilidine) for the test preparation. Corresponding values for the reference preparation were 24.95 ng/ml (tilidine) and 100.73 ng/ml (nortilidine). The extent of drug absorption (AUC0-infinity) amounted to 38.83 ng h/ml and 467.63 ng h/ml for the prodrug tilidine and the metabolite nortilidine of the test preparation and corresponded well to 43.81 ng h/ml and 493.85 ng h/ml of the reference. Regarding the rate of drug absorption, essentially identical tmax and Rabs values for both tilidine and nortilidine of either preparation in addition pointed to well comparable liquid formulations and equipotent analgesia may be inferred from opioid pharmakokinetic profiles. Pharmacokinetics of the opioid antagonist naloxone and 6-beta-naloxole were also determined and resulted in well coinciding profiles for both preparations. Thus despite the fact that only minimum oral naloxone bioavailabilities were observed, plasma level monitoring of naloxone and 6-beta-naloxole allowed for demonstration of systemic exposure of opioid antagonistic compounds throughout a period of 2-3 h after oral drug administration. Due to the limited number of subjects involved, the primary aim of the study did not consist in demonstration of drug bioequivalence. Rather a comparable bioavailability between preparations was assumed if AUC and Cmax point estimators of 90% confidence intervals would be contained within a 0.80-1.20 range. The study outcome revealed that all four investigated analytes met this requirement, whilst nortilidine pharmacokinetic parameters even fulfilled commonly accepted bioequivalence criteria, i.e. inclusion of 90% confidence intervals of AUC- and Cmax-ratios within acceptance limits of 80% and 125%. Increased data variation observed with bioavailability parameters of tilidine, naloxone and 6-beta-naloxole prevented their bioequivalence demonstration based on only 12 study participants. In conclusion, single doses of two different tilidine/naloxone 50 mg/4 mg liquid formulations revealed well comparable bioavailability for all 4 analytes investigated. Both treatments were fairly well tolerated. Most frequently reported adverse events were dizziness, headache and nausea, which all recovered without sequelae and necessity of concomitant treatment.
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PMID:Bioavailability investigation of a new tilidine/naloxone liquid formulation compared to a reference formulation. 1044 8

Twenty-four (24) Caucasian male subjects completed a single-blind, randomised, three-treatment, three-period, cross-over study. In each treatment phase, subjects received a single dose of 144 mg pipamperone dihydrochloride (CAS 2448-68-2) (equivalent to 120 mg pipamperone; CAS 1893-33-0) as either the reference product (3 x 40 mg tablets), test product A (3 x 40 mg tablets) or test product B (1 x 120 mg tablet). Each consecutive dosing was separated by a washout period of 14 days. Following each dosing, venous blood samples were collected over a period of 120 h for the determination of plasma pipamperone concentrations by high-performance liquid chromatography. The most common drug related adverse events, ranging from mild to moderate in intensity, were bloodshot eyes, nasal congestion, dry mouth, hypotension and dizziness. The geometric mean Cmax of pipamperone for both the reference product and test product A was 266 ng/ml and for test product B 263 ng/ml. The geometric mean AUC0-infinity was 3107 ng.h/ml for the reference product, 3229 ng.h/ml for test product A and 3108 ng.h/ml for test product B. The two test products were shown to be bioequivalent to the reference product with respect to all pharmacokinetic variables investigated.
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PMID:Pharmacokinetics of pipamperone from three different tablet formulations. 1210 42

The bioavailability of two rilmenidine tablet formulations was compared in healthy male (17) and female (8) subjects, aged 18 to 36 years, during a laboratory-blind, randomized, two-treatment, two-period, cross-over study under fasting conditions. In each treatment phase subjects received a single dose of 1.544 mg rilmenidine dihydrogen phosphate (CAS 85409-38-7), equivalent to 1 mg rilmenidine (CAS 54187-04-1). Consecutive dosing was separated by a drug-free wash-out period of 7 d. Following each dosing, serial venous blood samples were collected over a period of 48 h for the determination of plasma rilmenidine concentrations by means of a validated LCMS/MS method. The most frequently reported drug-related adverse events were dizziness and headache ranging from mild to moderate in intensity. The geometric mean C(max) of rilmenidine for the reference and test products was 3.73 and 3.97 ng/ml, respectively. The corresponding geometric mean AUC(0-infinity)) was 34.0 and 35.1 ng x h/ml. T(max) for both products under investigation appeared at 1.33 h. The test product was shown to be bioequivalent to the reference product with respect to all pharmacokinetic variables investigated.
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PMID:Bioequivalence evaluation of rilmenidine in healthy volunteers. 1953 23

Triflusal (CAS 322-79-2) is an antiplatelet agent that irreversibly acetylates cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), possesses also antiaggregant activity. Recently a new oral 600 mg (10 ml) solution form of triflusal has been developed. The purpose of this clinical trial was to study the relative bioavailability of the new oral solution of triflusal versus the capsules formulation, both administered as a single dose. This was a randomized, two-way, cross-over, open-label, single-site phase I clinical trial, in 24 healthy volunteers who received triflusal as 600 mg oral solution and as two 300 mg capsules in a single administration separated by a washout period of at least 17 days. Blood samples were collected and plasma concentrations of HTB were measured. Pharmacokinetic parameters used for bioequivalence assessment included AUC(0-t), AUC(0-inf) and Cmax. The formulations were considered bioequivalent if the geometric mean ratios of AUC(0-t), AUC(0-inf) and Cmax were within the predetermined equivalence range (80% to 125%). Tolerability was based on the recording of adverse events (AEs), physical examination, electrocardiogram (ECG) and laboratory tests. The parameters for bioequivalence, mean [SD] values were as follows: AUC(0-t) (microg x h/ml): 3574.08 [628.17] for triflusal oral solution and 3901.78 [698.43] for triflusal capsules; AUC(0-infinity) (microg x h/ml): 4089.21 [842.54] for triflusal oral solution and 4471.33 [905.93] for triflusal capsules; Cmax, (microg/ml): 91.24 [12.88] for triflusal oral solution and 88.61 [13.46] for triflusal capsules; Cmax/AUC(0-infinity) (h(-1)): 0.03 (0.00) for triflusal oral solution and 0.02 (0.00) for triflusal capsules. The 90% confidence intervals for the ratio experimental/control by analysis of variance after log transformed AUC(0-infinity), AUC(0-t), and Cmax were within 80% to 125%. Similar results were found for the data without log transformation. All adverse events were of mild or moderate intensity and all subjects recovered. Nine and 12 subjects reported at least one adverse event during treatment with triflusal oral solution and with triflusal capsules, respectively. The most frequently reported adverse events were headache and dizziness. It was concluded that the 600-mg solution of triflusal appeared to be bioequivalent to the reference formulation capsules. Both formulations were well tolerated.
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PMID:Comparative bioavailability study of triflusal oral solution vs. triflusal capsules in healthy subjects. A single, randomized, two-way cross-over, open-label phase I study. 2018 25