scholarly journals Efficacy and Safety of Oral Pleconaril for Treatment of Colds Due to Picornaviruses in Adults: Results of 2 Double-Blind, Randomized, Placebo-Controlled Trials

2003 ◽  
Vol 36 (12) ◽  
pp. 1523-1532 ◽  
Author(s):  
Frederick G. Hayden ◽  
Darrell T. Herrington ◽  
Teresa L. Coats ◽  
Kenneth Kim ◽  
Ellen C. Cooper ◽  
...  
Keyword(s):  
Ethinyl Estradiol ◽  
Controlled Trials ◽  
The Novel ◽  
Double Blind ◽  
Cholesterol Levels ◽  
Cold Symptom ◽  
Symptom Scores ◽  
Picornavirus Infection ◽  
Cytochrome P 450

Abstract The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients (P > .001). Cold symptom scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults.

Selected natural agents used for cholesterol controls

2018 ◽  
Vol 48 (2) ◽  
pp. 301-317 ◽  
Author(s):  
Nurul Hazwani Abdul Latif ◽  
Muhammad Taher ◽  
Juliana Md Jaffri ◽  
Mohamad Shahreen Amri ◽  
Muhammad Badri Abdul Kudos ◽  
...  
Keyword(s):  
Synthesis Process ◽  
Red Yeast Rice ◽  
Hypocholesterolemic Effect ◽  
Double Blind ◽  
Content Type ◽  
Natural Agents ◽  
Cholesterol Levels ◽  
Phytochemical Components ◽  
Positive Effect

Purpose Various studies suggest that some of natural agents create a specific action of hypocholesterolemic effect. Considering this fact, the aim of this paper is to work on describing selected natural agents that may reduce cholesterol concentrations by different mechanism of actions. Design/methodology/approach The advantages, phytochemical components and the mechanisms of the agents were reviewed and supported from the findings of the in vitro, double-blind and clinical studies from published journals, books and articles. The journals used in this review were published between 1987 and 2016, and are available from PubMed, ScienceDirect and Google Scholar. Findings Plant stanols and sterols, turmeric, fenugreek, avocado, tomato, artichoke, red yeast rice and garlic showed a positive effect in maintaining cholesterol levels by specific mechanisms or actions. These agents each had a specific action in creating a hypocholesterolemic effect either by inhibition of the enzyme significant to the synthesis process, disturbing the absorption of cholesterol, conversion of cholesterol to other related forms and through the reduction of the oxidative stress. Research limitations/implications However, this field still needs more studies as, currently, there is not any detailed information regarding the main active ingredients responsible for the mechanism to reduce cholesterol levels in humans. Originality/value This paper enlightens the authors’ understanding of some natural agents that have the potential to be used in controlling cholesterol.

scholarly journals SAT-013 Segesterone Acetate (SA) Serum Levels with a Statistical Model of Continued Use of the SA/Ethinyl Estradiol (EE) Contraceptive Vaginal System

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
James H Liu ◽  
David F Archer ◽  
James A Simon ◽  
Andrew M Kaunitz ◽  
Marlena Plagianos ◽  
...  
Keyword(s):  
Statistical Model ◽  
Ethinyl Estradiol ◽  
Serum Levels ◽  
The Novel ◽  
Individual Subject ◽  
Model Following ◽  
The Mean ◽  
Using Data ◽  
Continuous Use

Abstract The novel, ring-shaped, contraceptive vaginal system (CVS; Annovera™), contains 103 mg of SA and 17.4 mg of EE, and delivers a mean dose of SA 0.15/EE 0.013 mg/day. The CVS was designed to last thirteen cycles in a 21 day-in/7 day-out regimen. Objectives of these analyses were to determine the amount of SA/EE remaining in the CVS after 13 cycles of use and to estimate the SA level in serum after 1 year of continuous use. Residual SA/EE levels from CVS used by women (n=18) for 13 cycles of 21/7 regimen in a phase 3 clinical trial were further analyzed in vitro. Hypothetical SA level in serum after 1 year of continuous use was estimated using data from 39 women who participated in a 13-cycle pharmacokinetic study of the 21/7 CVS regimen. The serum data were used to construct a statistical model for the change in serum SA concentrations from cycle 1 to cycle 13. The data from each individual subject was modeled to estimate the serum SA level based on days of use. Each subject’s model was then used to estimate the serum SA level after 364 days of continuous CVS use. The average of all 364-day values from valid models was then calculated. After 13 cycles of a 21/7 regimen, the amount of SA/EE remaining in the CVS was 61.7 mg/14.0 mg (60%/80% of the original SA/EE load), which established the release of 0.15 mg SA and 0.013 mg EE per day for a total of 273 days. The model predicted that the mean serum SA level after 364 days of continuous use was 71 pmol/L with a lower limit of the 90% CI of 52 pmol/L. A high percentage of SA/EE remained in the CVS after 13 cycles of use. Serum SA levels predicted by the model following 1 year of continuous use were similar to those previously observed (mean 73 pmol/L) at 1 year in a SA silicone implant trial in which there were no reported pregnancies at 1 year (Sivin et al, Contraception. 2004;69:137-144). No pregnancy or PK data with continuous use of the CVS is available at this time. Further study on the continuous use of the CVS is warranted.

scholarly journals Current Thoughts on the Treatment of Malassezia in Canine Otitis Externa

2017 ◽  
Vol 2 (3) ◽  
Author(s):  
Mary Fraser
Keyword(s):  
Otitis Externa ◽  
Current Knowledge ◽  
Chelating Agent ◽  
Controlled Trials ◽  
Double Blind ◽  
Malassezia Pachydermatis ◽  
Pubmed Database ◽  
Significant Difference ◽  
Randomised Controlled

<p>Otitis externa is a commonly diagnosed disorder of canine patients (Rosser, 2004) and can be caused by a number of different factors including infection, allergy, foreign bodies and breed/ear conformation. Malassezia pachydermatis is a yeast which is found as a commensal on canine skin, but may also contribute to the development and perpetuation of the condition.</p><p>The aim of this paper was to assess current knowledge and approaches to the treatment of M. pachydermatis when found to be present in cases of canine otitis externa.</p><p>A literature search was carried out using PubMed database. Search terms Malassezia, dogs / canine, otitis and therapy/treatment/therapeutics were utilised. This identified 26 results from 2005 - 2015. Examination of these papers focussed the review to 11 papers that were clinically relevant. The excluded papers were either concerned with laboratory storage/growth of M. pachydermatis, did not include therapy of the condition, or focussed on other skin conditions.</p><p>Of the 11 papers deemed relevant to this study, only three were double blind, randomised controlled trials (Rougier et al, 2005, Bensignor &amp; Grandemange, 2006, Hensel et al, 2009); one paper was a review of current literature relating to dermatology, including otitis externa (Bond, 2010) and the remainder were focussed on in vitro work with M. pachydermatis.</p><p>Many different therapeutics were used, namely thiabendazole, amphotericin B, itraconazole, ketoconazole, clotrimazole, miconazole, nystatin, chelating agents and various ear cleaners.</p><p>Within the controlled trials, a chelating agent was shown to improve therapeutic effectiveness of topical medication, combination therapy (antifungal, antibacterial and anti-inflammatory agents) was more effective than antifungal agent alone and no significant difference was noted when comparing combination therapies. A clear difference was found between different ear cleaners.</p><p>This review highlights the variety of different medications that can be used in the treatment of Malassezia otitis externa and the need for a greater number of robust clinical trials.</p><p>Find out more about <a href="http://www.girlingandfraser.co.uk/page4.htm" target="_blank">Mary</a>.</p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" />

Insights from In Vitro and Clinical Data to Guide Transition from the Novel P2Y12 Antagonist Selatogrel to Clopidogrel, Prasugrel, and Ticagrelor

2021 ◽  
Author(s):  
Uta Schilling ◽  
Jasper Dingemanse ◽  
Michael Dobrow ◽  
Martine Baumann ◽  
Markus A. Riederer ◽  
...  
Keyword(s):  
P2y12 Receptor ◽  
Time Interval ◽  
Dependent Manner ◽  
The Novel ◽  
Receptor Antagonists ◽  
Open Label ◽  
Double Blind ◽  
Concentration Dependent Manner ◽  
P2y12 Receptor Antagonist

AbstractReduced pharmacodynamic (PD) effects of irreversible oral P2Y12 receptor antagonists have been reported when administered during cangrelor infusion. Therefore, the PD interaction liability of the novel P2Y12 receptor antagonist selatogrel with irreversible (i.e., clopidogrel, prasugrel) and reversible (i.e., ticagrelor) oral P2Y12 receptor antagonists was investigated in vitro and in healthy subjects. In vitro, selatogrel reduced the effects of clopidogrel and prasugrel in a concentration-dependent manner, while additive effects were observed for the combination of selatogrel and ticagrelor. Accordingly, a single-center, randomized, double-blind, two-way crossover study was conducted consisting of six groups. In each group (N = 12), an open-label loading dose of 300 or 600 mg clopidogrel, 60 mg prasugrel, or 180 mg ticagrelor was administered 30 minutes (i.e., at t max of selatogrel) or 12 hours after a single subcutaneous dose of 16 mg selatogrel or placebo. Inhibition of platelet aggregation (IPA) was assessed at various time points up to 48 hours. Reduced IPA was determined when clopidogrel or prasugrel was administered 30 minutes after selatogrel (∼40 and 70% lower IPA, respectively, at 24 hours postdosing). However, when administering prasugrel 12 hours after selatogrel, IPA was not impacted (>90% IPA) and in the case of clopidogrel reduced effects were partially mitigated. Similar IPA was determined for ticagrelor when administered 30 minutes after selatogrel or placebo. In conclusion, reduced IPA was observed for clopidogrel and prasugrel when administered after selatogrel, which can be mitigated by applying an appropriate time interval. No PD interaction with ticagrelor was observed.

Biotransformation of Mestranol to Ethinyl Estradiol In Vitro: The Role of Cytochrome P-450 2C9 and Metabolic Inhibitors

1997 ◽  
Vol 37 (3) ◽  
pp. 193-200 ◽  
Author(s):  
Jürgen Schmider ◽  
David J. Greenblatt ◽  
Lisa L. von Moltke ◽  
Dmitri Karsov ◽  
Richard Vena ◽  
...  
Keyword(s):  
Ethinyl Estradiol ◽  
Metabolic Inhibitors ◽  
Cytochrome P 450

Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽  
2005 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Brunner-La Rocca ◽  
Schindler ◽  
Schlumpf ◽  
Saller ◽  
Suter
Keyword(s):  
Endothelial Dysfunction ◽  
Blood Lipids ◽  
Ex Vivo ◽  
Hdl Cholesterol ◽  
Blood Lipid ◽  
Tibetan Medicine ◽  
Double Blind ◽  
Intraarterial Infusion ◽  
Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

1995 ◽  
Vol 74 (04) ◽  
pp. 1064-1070 ◽  
Author(s):  
Marco Cattaneo ◽  
Alan S Harris ◽  
Ulf Strömberg ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Meta Analysis ◽  
Postoperative Blood Loss ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Transfusion Requirements ◽  
The Mean ◽  
Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

The d-Enantiomer Form of Indobufen Totally Accounts for the Anti-Cyclooxygenase and Antiplatelet Activity Ex Vivo and for the Increase in Bleeding Time by Indobufen in Man

1992 ◽  
Vol 67 (02) ◽  
pp. 258-263 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
An Yan ◽  
Walter Bernini ◽  
Daniela Giannessi ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Random Sequence ◽  
Antiplatelet Agent ◽  
Antiplatelet Drug ◽  
Double Blind

SummaryIndobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean ± S.D., 58.7 ± 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 ±3% for both treatments). At 12 h inhibition was 87 ± 6% for d-indobufen and 88 ± 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs. Maximum inhibitory effect on aggregation was seen in response to collagen 1.5 pg/ml (63 ± 44% for d-indobufen and 81 ± 22% for dl-indobufen) and arachidonic acid 0.5-2 mM (78 ± 34% for d-indobufen and 88 ± 24% for dl-indobufen) at 2 h after each administration. An effect of both treatments on platelet aggregation after 12 h was present only for adrenaline 2 μM (55 ± 41% for d-indobufen and 37 ± 54% for dl-indobufen), collagen 1.5 pg/ml (69 ± 30% for d-indobufen and 51 ± 61% for dl-indobufen), arachidonic acid 0.5-2 mM (56 ± 48% for d-indobufen and 35 ± 49% for dl-indobufen). The extent of inhibition of TX production and the extent of residual platelet aggregation were never significantly different between treatments. Bleeding time prolongation was similar in the two treatment groups without showing a pronounced and long lasting effect (from 7.0 ± 2.0 min to 10.0 ± 3.0 min at 2 h and 8.0 ± 2.0 min at 12 h for d-indobufen; from 6.0 ±1.0 min to 8.5 ± 2.0 min at 2 h and 8.0 ± 1.0 min at 12 h for dl-indobufen). These results demonstrate that the biological activity of dl-indobufen as an antiplatelet agent in vivo is totally accounted for by d-indobufen.

The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

1967 ◽  
Vol 18 (03/04) ◽  
pp. 766-778 ◽  
Author(s):  
H. J Knieriem ◽  
A. B Chandler
Keyword(s):  
Platelet Count ◽  
Placebo Group ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Platelet Rich Plasma ◽  
Healthy Adults ◽  
Double Blind Study ◽  
Double Blind ◽  
Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
Author(s):  
Ulf Berglund ◽  
Henning von Schenck ◽  
Lars Wallentin
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Controlled Study ◽  
Double Blind ◽  
Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

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