• The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity. (wikipedia.org)
  • To account for delays between exposure and toxicity, the TI for toxicities that occur after multiple dose administrations should be calculated using the exposure to drug at steady state rather than after administration of a single dose. (wikipedia.org)
  • The primary endpoints of the phase 1 were dose limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetic parameters. (nih.gov)
  • A single dose-limiting toxicity, a grade 5 hypoxia event, occurred in a patient who had treatment-unrelated fungal pneumonia and sepsis. (cancernetwork.com)
  • Both species tolerated the exposures without overt signs of toxicity. (cdc.gov)
  • The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. (knowcancer.com)
  • BIND-014 was generally safe and well-tolerated with transient and manageable neutropenia as the dose limiting toxicity. (tgen.org)
  • One study with 10 patients concluded that tumescent anesthesia with a lidocaine dose of 55 mg/kg is safe for liposuction.1 We have personally performed tumescent liposuction on more than 400 patients using lidocaine doses in the range of 50-60 mg/kg without evidence of lidocaine toxicity. (liposuction.com)
  • Subjects in Part 1 (Dose Escalation) will receive escalating doses of CB-03-10 based on a modified Fibonacci schema using a standard oncology 3+3 study design to define an MTD and a RP2D. (ucbraid.org)
  • however, the benefits of escalation to a maximum tolerated dosage (MTD) over a fixed or low-dose approach to therapy, remains controversial. (ashpublications.org)
  • In the phase 1 portion of the study, patients received CH5424802 orally twice daily by dose escalation. (nih.gov)
  • In a phase I dose-escalation trial, 25 of 45 patients (56%) responded to the treatment, including six complete remissions. (cancernetwork.com)
  • OUTLINE: This is a dose-escalation study of vinorelbine. (knowcancer.com)
  • Steroids are the standard first line treatment, with either 6‐week courses of tapering prednisone or repeated courses of high dose dexamethasone providing equivalent efficacy. (mja.com.au)
  • In the phase 2 portion of the study, patients received CH5424802 at the recommended dose identified in the phase 1 portion of the study orally twice a day. (nih.gov)
  • In the phase 1 portion, 24 patients were treated at doses of 20-300 mg twice daily. (nih.gov)
  • In the phase 2 portion of the study, 46 patients were treated with the recommended dose, of whom 43 achieved an objective response (93.5%, 95% CI 82.1-98.6) including two complete responses (4.3%, 0.5-14.8) and 41 partial responses (89.1%, 76.4-96.4). (nih.gov)
  • CH5424802 is well tolerated and highly active in patients with advanced ALK-rearranged NSCLC. (nih.gov)
  • At the highest dose level evaluated (70 mg/m(2)), zero of six patients had DLT. (nih.gov)
  • this recipe has been used in clinical practice, particularly for patients requiring small doses (e.g., young children). (pdr.net)
  • Renal Impairment: For patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, halve usual initial dose. (nih.gov)
  • Studies in special risk groups (elderly, renally or hepatically impaired patients) indicate that it is not necessary to adjust the dose of fexofenadine hydrochloride in these patients. (medicines.org.uk)
  • Combination treatment provides better response and control of the disease and is often used in patients with advanced or metastatic disease who clinically are able to tolerate this approach. (medscape.com)
  • Cohorts of 3 to 6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. (knowcancer.com)
  • Based on our results showing EPOCH to be effective and well tolerated, we began a phase II study of EPOCH in previously untreated patients with aggressive lymphomas. (cancer.gov)
  • In this study, EPOCH doses are escalated within patients to the maximum tolerated dose (MTD). (cancer.gov)
  • Patients were able to tolerate 100 percent of the planned dose intensity. (cancer.gov)
  • As of November 14, 2023, 15 patients with rGBM have been treated with rhenium ( 186 Re) obisbemeda at a dose of 22.3 mCi delivered directly to the tumor by Convection Enhanced Delivery (CED). (wreg.com)
  • The average percent of treated tumor across all 15 patients was 87.2% at 120 hours, with 13/15 patients receiving greater than or equal 70% tumor volume coverage by the drug and ≥100 Gy absorbed dose to the tumor. (wreg.com)
  • In 28 patients with advanced or metastatic solid tumors, BIND-014 - with its targeted docetaxel Accurin - was shown to be generally safe and well-tolerated at the established maximum dose of 60 mg/m2. (tgen.org)
  • This Phase 1 trial has successfully established the safety and tolerability profile and maximum tolerated dose of BIND-014 in patients with advanced or metastatic solid tumor cancers," said Dr. Von Hoff, F.A.C.P., TGen's Distinguished Professor. (tgen.org)
  • The safety of such high doses has yet to be well documented by rigorous pharmacologic studies involving a large number of patients. (liposuction.com)
  • Determine the maximum tolerated dose and dose-limiting toxic effects of recombinant fowlpox-TRICOM vaccine in patients with advanced squamous cell carcinoma of the oral cavity or oropharynx or nodal or dermal metastases. (knowcancer.com)
  • Azithromycin is frequently used alone or in combination with other antimicrobial drugs to treat these syndromes because of its activity against Chlamydia trachomatis and its long tissue half-life, enabling single-dose administration. (cdc.gov)
  • Recent work has demonstrated the selection of MRM during single-dose and multidose treatment with azithromycin ( 11 - 13 ). (cdc.gov)
  • For animals in pre-clinical trials, Therapeutic Index = L D 50 E D 50 {\displaystyle {\text{Therapeutic Index}}=\mathrm {\frac {LD_{50}}{ED_{50}}} } For humans in clinical trials, Therapeutic Index = T D 50 E D 50 {\displaystyle {\text{Therapeutic Index}}=\mathrm {\frac {TD_{50}}{ED_{50}}} } For many drugs, severe toxicities in humans occur at sublethal doses, which limit their maximum dose. (wikipedia.org)
  • All participants received hydroxyurea therapy escalated to a stable MTD, which was defined by moderate myelosuppression (typically ANC of 2,000-4,000 x 10 6 /L) and no dose-limiting toxicities. (ashpublications.org)
  • To determine the maximum-tolerated or recommended phase II dose, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and immunomodulatory effects of lenalidomide in children with recurrent or refractory solid tumors or myelodysplastic syndrome (MDS). (nih.gov)
  • Classically, in clinical indication settings for an approved drug, TI refers to the ratio of the dose of drug that causes adverse effects at an incidence/severity not compatible with the targeted indication (e.g. toxic dose in 50% of subjects, TD50) to the dose that leads to the desired pharmacological effect (e.g. efficacious dose in 50% of subjects, ED50). (wikipedia.org)
  • Clinical trials utilizing hydroxyurea at MTD reported higher fetal hemoglobin (HbF) levels (~20% versus ~15%) compared to those with a fixed lower-dose (Ware, Blood 2010). (ashpublications.org)
  • A clinical drug-drug interaction study showed that co-administration of apalutamide (a weak inducer of P-gp) and a single oral dose of 30 mg fexofenadine resulted in a 30 % decrease in AUC of fexofenadine. (medicines.org.uk)
  • There were no dose related alterations in clinical chemistry. (cdc.gov)
  • The authors conclude that MAK does not produce cardiopulmonary or clinical chemical changes at the doses studied. (cdc.gov)
  • This regimen is based on experimental/clinical observations that suggest infusion schedules may improve the therapeutic index of natural product-derived cytotoxics, and that high-dose alkylator therapy can overcome drug resistance in lymphoma. (cancer.gov)
  • Our 2024 focus will be onboarding additional clinical sites, completing Phase 2 enrollment, continuing the Phase 1 trial to maximum tolerated dose, and planning next steps for the program. (wreg.com)
  • They should also help to determine whether or not the effects vary with dose and/or duration, and place into perspective the possible significance of these effects to human health. (cdc.gov)
  • A higher therapeutic index is preferable to a lower one: a patient would have to take a much higher dose of such a drug to reach the toxic threshold than the dose taken to elicit the therapeutic effect. (wikipedia.org)
  • BIND-014 represents the first targeted and programmable Accurin nanomedicine to reach the clinic from BIND's proprietary drug development platform, which creates targeted therapeutics designed to accumulate at the site of disease for high drug concentration and maximum therapeutic effect. (tgen.org)
  • The study also showed that the extent and duration of the therapeutic effect was dose-dependent, reaching maximum effectiveness and duration at 2,000 mg. (medicalxpress.com)
  • 0.001) In April 2020, FDA approved additional dosing of 400 mg q6wk for up to 1 year. (medscape.com)
  • thus 300 mg twice daily was the recommended phase 2 dose. (nih.gov)
  • LBR-101 has successfully completed five Phase I trials with 94 healthy volunteers dosed with active drug. (tevapharm.com)
  • A sixth Phase 1 study (bridging study) tested IV and subcutaneous doses (24 participants received active medication). (tevapharm.com)
  • Rhenium ( 186 Re) obisbemeda continues to be generally safe and well tolerated, consistent with data accumulated in the Phase 1 trial. (wreg.com)
  • Both intravenous and subcutaneous administrations were well tolerated. (tevapharm.com)
  • In life‐threatening bleeding, we recommend platelet transfusions to achieve haemostasis, along with intravenous immunoglobulin and high dose steroids. (mja.com.au)
  • In each group, six participants received intravenous infusions over six hours with various doses of the drug (ranging from 62.5 milligrams (mg) to 2,000 mg). (medicalxpress.com)
  • These considerations emphasize the importance of using exposure instead of dose to calculate TI. (wikipedia.org)
  • In the early days of pharmaceutical toxicology, TI was frequently determined in animals as lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50). (wikipedia.org)
  • The lowest lethal doses of diethyl phthalate in rabbits and guinea pigs administered the compound by gavage were determined to be 4,000 and 5,000 mg/kg, respectively (Smyth and Smyth 1931). (cdc.gov)
  • Initially, 25-100 mg orally at bedtime or give in divided doses. (globalrph.com)
  • It was concluded that deoxyribonuclease, batch U8AGS, formulated in phosphate buffered saline did not induce micronuclei in the polychromatic erythrocytes of the bone marrow of male mice when dosed intravenously with up to 400 mg/kg/day (an estimate of the maximum tolerated dose for this study), under the experimental conditions employed. (europa.eu)
  • No deaths were observed when diethyl phthalate was incorporated into the diet of mice for 2 weeks at doses of up to 6,500 mg/kg/day. (cdc.gov)
  • Much of what is seen and discussed in Maximum Tolerated Dose applies to all species used in this way- laboratory animals are reduced to a mere means of obtaining data and research papers. (bestvegandocumentaries.com)
  • Mild to moderate hepatic impairmen t: Use with caution and/or reduced dose/frequency. (globalrph.com)
  • Generally, a drug or other therapeutic agent with a narrow therapeutic range (i.e. having little difference between toxic and therapeutic doses) may have its dosage adjusted according to measurements of its blood levels in the person taking it. (wikipedia.org)
  • To the best of my knowledge, that was the first documented case of tumescent liposuction totally by local anesthesia where a standard dose of lidocaine, widely recognized as safe, has led to potentially toxic plasma lidocaine concentrations. (liposuction.com)
  • A procedure in which physicians replace marrow destroyed by high doses of anti-cancer drugs or radiation. (ucsfhealth.org)
  • Subjects in Part 2 (Dose Expansion) of the study will receive CB-03-10 at the RP2D determined in the Part 1 of the study. (ucbraid.org)
  • Comment on any additional information that should be included regarding the Maximum Tolerated Dose discussion in the rat chronic inhalation study. (cdc.gov)
  • However, this study is limited in that only two to six animals were tested at each dose level and no control data were presented. (cdc.gov)
  • In general, it is the exposure of a given tissue to drug (i.e. drug concentration over time), rather than dose, that drives the pharmacological and toxicological effects. (wikipedia.org)
  • For example, at the same dose there may be marked inter-individual variability in exposure due to polymorphisms in metabolism, DDIs or differences in body weight or environmental factors. (wikipedia.org)
  • The points in the figure showing no-observed-adverse-effect levels (NOAELs) or lowest observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. (cdc.gov)
  • GLPG1972 was rapidly absorbed (median time to maximum concentration, 4 hours), and eliminated with a mean apparent terminal elimination half-life of ≈10 hours. (lu.se)
  • Area under the plasma concentration-time curve (56.8-67.6 μg · h/mL) and time to maximum concentration (4 hours) were similar between studies. (lu.se)
  • Concentrations were tested up to 8333 μg enzyme concentrate dry matter/mL), a recommended regulatory maximum concentration for the in vitro micronucleus assay. (europa.eu)
  • Chronic pain (adjunct): Initially, 25 mg at bedtime - may increase as tolerated to 100 mg/day. (globalrph.com)
  • Steady state was achieved within 2 days of dosing, with minimal accumulation. (lu.se)
  • We have recently developed and tested a "second generation" EPOCH regimen (EPOCH II) to replace stem cell transplant for lymphomas requiring high-dose intensity, including poor prognosis untreated aggressive lymphomas, potentially curable relapsed lymphomas, and low-grade lymphomas. (cancer.gov)
  • Hypertension: Initial adult dose is 10 mg once daily. (nih.gov)
  • Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. (cdc.gov)
  • 14 days) ascending oral (tablet) doses of GLPG1972 in healthy Japanese and White men (N = 88). (lu.se)
  • Gradually increase to usual effective dose of 50 to 300mg/day. (globalrph.com)
  • In addition to confirming the safety, tolerability and maximum tolerated dose of BIND-014, these data also provide encouraging signs of anti-tumor activity in a variety of solid tumors," said Dr. Gregory Berk, Chief Medical Officer of BIND Therapeutics. (tgen.org)
  • Dosage and volume of the injection(s) depend on whether it is the initial dose, second dose, or subsequent doses and by lesion size. (medscape.com)
  • Cohorts of children with solid tumors received lenalidomide once daily for 21 days, every 28 days at dose levels of 15 to 70 mg/m(2)/dose. (nih.gov)
  • The recommended dose of fexofenadine hydrochloride for adults is 180 mg once daily taken before a meal. (medicines.org.uk)
  • This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. (cdc.gov)
  • The recommended dose of Prozac is 10-80 mg daily. (rxlist.com)
  • Studies did not show a benefit in the treatment of depression at doses higher than 40 mg per day. (globalrph.com)
  • Higher than recommended dosing or repeated dosing appears to increase the risk. (nih.gov)
  • In the presence of 10% rat liver S9, doses up to 7,500 μg/plate did not induce an increase in mutant colonies in TA100. (europa.eu)
  • GLPG1972 was generally well tolerated at all doses. (lu.se)
  • SSRIs in general, are better tolerated than many other medicines used in the treatment of depression. (drugs.com)
  • Our results are quite encouraging because they show the candidate compound is well-tolerated at doses even twice as high as the ones targeted for a future treatment and without any signs of bleeding," Jandrot-Perrus said. (medicalxpress.com)
  • 2015) who compared imepitoin high (30 mg/kg BID) to low (1 mg/kg BID) doses and concluded that doses of 30 mg/kg BID are effective in managing seizures in dogs with idiopathic epilepsy. (ivis.org)
  • The drug was well-tolerated at all doses, without serious side effects. (medicalxpress.com)
  • Multiple dosing significantly reduced ARGS levels vs baseline at all time points for all doses vs placebo. (lu.se)
  • The increases in TA97 revertants were dose-related and reached 5-6-fold control levels at 800 µM, which is clearly biologically and statistically significant. (europa.eu)
  • Fecal excretion through 72 hours represented less than 2 percent of the administration dose. (cdc.gov)
  • No data from individual concentrations was presented, only the slope (revertants/µg) at the linear part of the dose-response curve. (europa.eu)
  • In strain TA98 without S9, cobalt metal (100 to 3,500 μg/plate) was mutagenic, although the responses observed were weak and not well correlated with dose level. (europa.eu)
  • Lenalidomide is well-tolerated at doses up to 70 mg/m(2)/d for 21 days in children with solid tumors. (nih.gov)