A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.
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ABSTRACT:
SUBMITTER: Kurosawa Y
PROVIDER: S-EPMC4479826 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
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Project description:Objective: This study evaluated associations of estradiol (E2) dose and serum E2 levels with coagulation/anti-coagulation measures in early (<6 years) compared with late (≥10 years) postmenopausal women.Methods: Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models tested the association of E2 dose and serum E2 levels with the prothrombin time (PT), the activated partial thromboplastin time (APTT), antithrombin (ATHRM), fibrinogen (FIBRINO), protein C (PROTC), and protein S (PROTS), assessed five times over 12 months.Results: Among 1215 early and 297 late postmenopausal women, the E2 dose was statistically significantly inversely associated with the APTT in early postmenopause, PROTC in late postmenopause, and with the PT, ATHRM, and PROTS in both groups. Serum E2 levels were statistically significantly inversely associated with the APTT, PROTS, and FIBRINO in early postmenopause, the PT in late postmenopause, and ATHRM and PROTC in both groups. With longer time since menopause, the inverse E2 dose effect and serum E2 effects became stronger.Conclusion: Increasing E2 dose and serum E2 levels were associated with changes in coagulation/anti-coagulation measures. The associations were stronger among women ≥10 years since menopause when initiating E2. The timing of E2 therapy, E2 dose, and serum E2 levels relative to time since menopause may modify the venous thromboembolism risk.
| S-EPMC7853766 | biostudies-literature
Project description:Introduction Amenamevir (ASP2151), a herpesvirus helicase-primase inhibitor, is currently used for the treatment of herpes zoster in Japan. Amenamevir is mainly metabolized in the liver, and urinary excretion of amenamevir is approximately 10% in healthy adults. The increase of systemic exposure in non-dialysis patients with severe renal impairment was much less than that associated with nucleoside antiviral agents. The aim of this study was to evaluate the pharmacokinetics and dialyzability of a single oral dose (400 mg) of amenamevir in hemodialysis patients. Methods This was a single-arm, open-label, multicenter clinical pharmacology study. Nine patients aged 20–80 years with end-stage kidney disease and undergoing maintenance hemodialysis three times weekly were enrolled. Pharmacokinetics and dialyzability were investigated by serial collection of blood samples until 48 h post-dose during the study. Results The maximum plasma concentration and time to reach maximum plasma concentration during 24 h post-dose were 1585 ng/mL and 6.2 h, respectively. The area under the plasma concentration–time curve (AUC) from time zero to 24 h was 23,890 ng h/mL. The median terminal elimination half-life within 24 h before, during, and after hemodialysis was 14.7, 15.2, and 12.4 h, respectively. The AUC in hemodialysis patients was approximately double that in healthy adults. This increase in AUC was much less than that reported in nucleoside antiviral agents. The hemodialysis clearance, elimination fraction percentage, and amount of amenamevir removed were 37.8 mL/min, 28.1%, and 132.0 ?g, respectively. The amount of amenamevir removed by hemodialysis was minimal. None of the hemodialysis parameters were associated with serum albumin. This study revealed no clinically relevant safety concerns. Conclusion There were no clinically relevant safety concerns when 400 mg of amenamevir was administered as a single dose to hemodialysis patients without dose adjustment and/or modification of the dosing schedule. Trial Registration JapicCTI-184242. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01375-1) contains supplementary material, which is available to authorized users.
| S-EPMC7547951 | biostudies-literature
Project description:IntroductionAmenamevir (ASP2151), a herpesvirus helicase-primase inhibitor, is currently used for the treatment of herpes zoster in Japan. Amenamevir is mainly metabolized in the liver, and urinary excretion of amenamevir is approximately 10% in healthy adults. The increase of systemic exposure in non-dialysis patients with severe renal impairment was much less than that associated with nucleoside antiviral agents. The aim of this study was to evaluate the pharmacokinetics and dialyzability of a single oral dose (400 mg) of amenamevir in hemodialysis patients.MethodsThis was a single-arm, open-label, multicenter clinical pharmacology study. Nine patients aged 20-80 years with end-stage kidney disease and undergoing maintenance hemodialysis three times weekly were enrolled. Pharmacokinetics and dialyzability were investigated by serial collection of blood samples until 48 h post-dose during the study.ResultsThe maximum plasma concentration and time to reach maximum plasma concentration during 24 h post-dose were 1585 ng/mL and 6.2 h, respectively. The area under the plasma concentration-time curve (AUC) from time zero to 24 h was 23,890 ng h/mL. The median terminal elimination half-life within 24 h before, during, and after hemodialysis was 14.7, 15.2, and 12.4 h, respectively. The AUC in hemodialysis patients was approximately double that in healthy adults. This increase in AUC was much less than that reported in nucleoside antiviral agents. The hemodialysis clearance, elimination fraction percentage, and amount of amenamevir removed were 37.8 mL/min, 28.1%, and 132.0 μg, respectively. The amount of amenamevir removed by hemodialysis was minimal. None of the hemodialysis parameters were associated with serum albumin. This study revealed no clinically relevant safety concerns.ConclusionThere were no clinically relevant safety concerns when 400 mg of amenamevir was administered as a single dose to hemodialysis patients without dose adjustment and/or modification of the dosing schedule.Trial registrationJapicCTI-184242.
| S-EPMC7467425 | biostudies-literature
Project description:The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23?g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25?Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10??m, respectively, compared to 200??m in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25?Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25?Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1?mL of 0.9% saline/6?h for 24?h yielded a 100% survival only with 18?Gy self-resolved RIOM, which had 5.6?±?0.3?days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival.
| S-EPMC4921469 | biostudies-literature
Project description:BackgroundEach direct oral anticoagulant (DOAC) has different dose reduction criteria. Here, we evaluated the differences in the doses of three anti-Xa DOACs and clinical events based on the dose reduction criteria in patients with atrial fibrillation (AF).MethodsConsecutive AF patients prescribed with anti-Xa DOACs [rivaroxaban (Riva), apixaban (Apix), and edoxaban (Edox)] between April 2011 and May 2016 were retrospectively evaluated. The incidences of thromboembolic and bleeding events were evaluated by the end of December 2020, focusing on the dose proportion.ResultsA total of 786 patients (72 ± 10 years old, 66.9% male) were enrolled in this study [Riva (n = 337), Apix (n = 239), and Edox (n = 210)]. The proportion of reduced dose prescriptions was significantly greater for Edox (79.2%) than Riva (38.7%) or Apix (31.9%). A Kaplan-Meier analysis showed that the incidence of minor bleeding was significantly higher in the Apix than other groups (p < .001), even after propensity score matching. The standard dose of Apix had significantly higher bleeding events than the other DOACs (p < .001). Moreover, 23.2% and 51.6% of the patients with a standard dose of Apix were fulfilled with the dose reduction criteria for Riva and Edox and had more minor bleeding events than the unfulfilled ones (p = .046).ConclusionsThe patients with a standard dose of Apix had a higher incidence of minor bleeding events than the other dosages. A reduced dose of apixaban was not prone to being chosen because of the dose reduction criteria, which may have been associated with a higher minor bleeding rate in patients with Apix.
| S-EPMC9237315 | biostudies-literature
Project description:BACKGROUND:This is an update of a review published in The Cochrane Library 2008, Issue 4. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier reviews. OBJECTIVES:To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The most recent search was to 3 January 2012. SELECTION CRITERIA:We included randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain. DATA COLLECTION AND ANALYSIS:Two review authors assessed studies for quality and extracted data. We converted summed pain relief (TOTPAR) or pain intensity difference (SPID) into dichotomous information, yielding the number of participants with at least 50% pain relief over four to six hours, and used this to calculate the relative benefit (RB) and number needed to treat to benefit (NNT) for one patient to achieve at least 50% of maximum pain relief with celecoxib who would not have done so with placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. MAIN RESULTS:Eight studies (1380 participants) met the inclusion criteria. We identified five potentially relevant unpublished studies in the most recent searches, but data were not available at this time. The number of included studies therefore remains unchanged.The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% of maximum pain relief over four to six hours was 4.2 (95% confidence interval (CI) 3.4 to 5.6) and 2.5 (2.2 to 2.9) respectively. The median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 with celecoxib 400 mg, and 2.3 hours with placebo. The proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (3.5 to 7.7) and 3.5 (2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. Adverse events were generally mild to moderate in severity, and were experienced by a similar proportion of participants in celecoxib and placebo groups. One serious adverse event probably related to celecoxib was reported. AUTHORS' CONCLUSIONS:Single-dose oral celecoxib is an effective analgesic for postoperative pain relief. Indirect comparison suggests that the 400 mg dose has similar efficacy to ibuprofen 400 mg.
| S-EPMC4161494 | biostudies-literature
Project description:BackgroundDiclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'.ObjectivesTo assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015.Selection criteriaRandomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults.Data collection and analysisTwo review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects.Main resultsThis update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously. This is a result of increased understanding of the importance of speed of onset in determining analgesic efficacy in acute pain.The largest body of information, for diclofenac potassium 50 mg, in seven studies, produced an NNT for at least 50% of maximum pain relief compared with placebo of 2.1 (95% confidence interval (CI) 1.9 to 2.5) (high quality evidence). There was a graded improvement in efficacy as doses rose from 25 mg to 100 mg, both for participants achieving at least 50% maximum pain relief, and for remedication within 6 to 8 hours. Fast-acting formulations (dispersible products, solutions, and softgel formulations) had a similar efficacy for a 50 mg dose, with an NNT of 2.4 (2.0 to 3.0). Diclofenac sodium in a small number of studies produced a lesser effect, with an NNT of 6.6 (4.1 to 17) for the 50 mg dose.Adverse event rates were low in these single dose studies, with no difference between diclofenac and placebo (moderate quality evidence).Authors' conclusionsDiclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.
| S-EPMC6485701 | biostudies-literature
Project description:Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with new diagnostic targets and therapeutic strategies hold promise for more effective individualized anti-coagulation and anti-platelet therapy.
| S-EPMC3809070 | biostudies-literature
Project description:AIMS:Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptives (OC) on the pharmacokinetics of the protease inhibitor saquinavir. METHODS:Saquinavir was administered in a hard gelatin capsule formulation (Invirase) to rule out confounding by pharmaceutical aids of the more frequently used soft gelatin capsule. After an overnight fast, eight healthy female participants ingested a single oral dose of 600 mg saquinavir immediately before and after the 19th dose of a combined, low dose OC (0.03 mg ethinylestradiol, 0.075 mg gestodene) in a prospective, fixed sequence study design. The first saquinavir application was scheduled on day 1, 2, or 3 of the individual menstrual cycle. Plasma concentrations of saquinavir and relative concentrations of its M2&M3-hydroxy metabolites were determined by LC/MS/MS for 48 h. RESULTS:Intake of OC resulted in a significant decrease in morning serum concentrations (before intake of OC, compared to day 19 of OC therapy) of 17beta-estradiol by -23.4 pg ml-1 (57%, 95%CI: -76% to -37.4%); progesterone by -0.25 ng ml-1 (33%, 95%CI: -45.3% to -21.5%); follicle-stimulating hormone by -4.06 U l-1 (82%, 95%CI: -96.5% to -67.7%); and luteinizing hormone by -3.49 U l-1 (74%, 95%CI: -93 to -54.6%). Conversely, sexual hormone binding globulin serum concentrations increased by 83.6 nmol l-1 (205%, 95%CI: 32.2% to 377%). Pharmacokinetic parameters of saquinavir (AUC, Cmax, tmax, t1/2, CLR) were not affected by OC, nor was the relative metabolic ratio of saquinavir/M2&M3-hydroxy saquinavir. Furthermore, there was no association of serum hormone concentrations or MDR1-polymorphisms (C3435T and G2677T) with pharmacokinetic parameters of saquinavir. CONCLUSIONS:There was no effect of OC on saquinavir pharmacokinetics. Thus, pharmacokinetic interactions of synthetic sexual steroids with saquinavir are not likely to account for the increased ADR to antiretroviral therapy seen in women.
| S-EPMC1884449 | biostudies-literature
Project description:RationaleInteroception is the signalling, perception, and interpretation of internal physiological states. Many mental disorders associated with changes of interoception, including depressive and anxiety disorders, are treated with selective serotonin reuptake inhibitors (SSRIs). However, the causative link between SSRIs and interoception is not yet clear.ObjectivesTo ascertain the causal effect of acute changes of serotonin levels on cardiac interoception.MethodsUsing a within-participant placebo-controlled design, forty-seven healthy human volunteers (31 female, 16 male) were tested on and off a 20 mg oral dose of the commonly prescribed SSRI, citalopram. Participants made judgements on the synchrony between their heartbeat and auditory tones and then expressed confidence in each judgement. We measured three types of interoceptive cognition.ResultsCitalopram increased cardiac interoceptive insight, measured as correspondence of self-reported confidence to the likelihood that interoceptive judgements were actually correct. This effect was driven by enhanced confidence for correct interoceptive judgements and was independent of measured cardiac and reported subjective effects of the drug.ConclusionsAn acute change of serotonin levels can increase insight into the reliability of inferences made from cardiac interoceptive sensations.
| S-EPMC9205807 | biostudies-literature