Looking for pharmacokinetics software researchgate. This was a phase i, openlabel doseescalation study to evaluate the safety and tolerability of two different dose schedules of ixabepilone weekly and every 3 weeks, in combination with a fixed dose of sunitinib in patients with solid tumors previously treated with up to 4 prior systemic therapy regimens. Dose reduction is required in certain patients with elevated ast, alt, or bilirubin 2. Each specific drug example saved as excel file that can be used as template for your own. These models were derived for iv ixabepilone and then adjusted for oral dosing based on preliminary pharmacokinetic data from study ca163088 data not published but available online. Pharmacokinetics of ixabepilone was investigated in rat, mouse and dog, species used in toxicology. A phase i clinical, pharmacokinetic, and pharmacodynamic study. Ixabepilone auc and c max also showed correlations r 2 0. Ixempra ixabepilone for injection is supplied as a sterile, nonpyrogenic, singleuse vial providing 15 mg or 45 mg ixabepilone as a lyophilized white powder. A phase iii and pharmacokinetic trial of ixabepilone was conducted in patients with recurrent highgrade gliomas. Splus, r is considered for performing pre and postprocessing, where nonmem software handles the analyses portion. Ixempra pharmacokinetics absorption bioavailability. Patients with advanced solid malignancies were treated with escalating doses of carboplatin plus ixabepilone administered on day 1 schedule a or days 1 and 8.
Ixempra may also be used for purposes not listed in this medication guide. The bioavailability of ixabepilone in this oral formulation from study ca163088 was 43%, with cmax 50. Im now working with a mixed model lme in r software. A phase iii and pharmacokinetic trial of ixabepilone was conducted in. This video will show steps for calculation of pk parameters using r.
The pknca r package is designed to perform all noncompartmental analysis nca calculations for pharmacokinetic pk data. A phase i and pharmacokinetic study of ixabepilone in. Pkstamp pharmacokinetic sampling times allocation matlab platform is a library compiled as a single executable file, which does not. In this post i want to analyze a first order pharmocokinetcs problem. Ixabepilone demonstrated potent cytotoxicity in a broad range of human cancer cell lines in vitro and in a wide range of xenografts in vivo. Ixabepilone was designed through medicinal chemistry to improve upon these properties pharmacology.
Methods and software tools for design evaluation in. A graphical user interface gui package using the r software pfim interface is also available but does not include recent methodological developments. Choice of environment, language, or package is generally dependent on tools availability, cost, ease of use, and expertise. Ixempra ixabepilone for injection is intended for intravenous infusion only after constitution with the supplied diluent and after further dilution with a specified infusion fluid see instructions for preparation and iv administration. Which is the best package for analysis of pharmacokinetic. We conducted a randomized twoarm phase ib clinical trial of ascending doses of vorinostat and ixabepilone in prior treated mbc patients. Montero1, deukwoo kwon2, aurea flores1, krisztina kovacs1, jonathan c. Adult patients received ixabepilone as a 1h infusion daily for 5 days every 3 weeks. Constituted solution must be diluted with lactated ringers injection, usp, to a final ixabepilone concentration of 0. Preclinical efficacy spectrum and pharmacokinetics of. Which pk pharmacokinetic software is most widely used by. Read 36 answers by scientists with 20 recommendations from their colleagues to the question asked by roland j. Ixempra binds directly to betatubulin subunits and suppresses their dynamic instability, blocking the mitotic phase of the cell division cycle and inducing cell.
Calculate pharmacokinetic parameters using r youtube. Ixabepilone and carboplatin for hormone receptor positiveher2. The ixabepilone concentration in constituted solution is 2 mgml. Trent1, pasquale benedetto1, caio rochalima1, and jaime r. R pharm acquires ixempra r ixabepilone from bristolmyers squibb and launches u. Ixempra is used in the treatment of metastatic or locallyadvanced breast cancer. R pharm us was founded in 2014 with the goal of acquiring and commercializing products that help patients suffering from cancer and immunology conditions. A simple but easytouse menudriven package created for data analysis of ivivc. The original question then continues as i want to see a list of the most widely used pkpd software pharmacokinetic that is used by big pharma and biotech. Analysis of pharmacokinetic pk data is concerned with defining the relationship between the dosing regimen and the bodys exposure to drug as indicated by the concentration time curve to determine a dose. Not known if ixabepilone is distributed into human milk. Peak concentrations usually attained at end of 3hour infusion. Phase ib trial of ixabepilone and vorinostat in metastatic.
Ixempra ixabepilone is a prescription medicine used to treat locally advanced or metastatic breast cancer when certain other medicines have not worked or no longer work. Ixempra is classified as an antimicrotubule agent or an epothilone b analog. To determine the recommended phase ii dose of combination ixabepilone plus carboplatin based on the maximum tolerated dose, pharmacokinetics, optimum schedule, and safety. The r project for statistical computing getting started. Ixempra ixabepilone is used to treat advanced breast cancer. The pharmacokinetic profile of ixabepilone in adults was. Ixempra definition of ixempra by medical dictionary. A phase i clinical, pharmacokinetic, and pharmacodynamic. Ixabepilone is an epothilone, a novel class of nontaxane microtubule stabilizing agents.
Ixempra withdrawal assessment report european medicines. R is a free software environment for statistical computing and graphics. It compiles and runs on a wide variety of unix platforms, windows and macos. The final solution must be used within 6 hours of preparation. To evaluate the pharmacokinetic profiles of the combination of ixabepilone and sunitinib malate and correlate them with activity andor toxicity. The pharmacokinetic profile of ixabepilone was established in mice and humans. The recommended dose of ixempra is 40 mgm2 infused intravenously over 3 hours every 3 weeks 2. User friendly pk and graphical software with built in physiologically based pharmacokinetic, deconvolution, noncompartment pk and much more. Bristolmyers squibb, a cytotoxic microtubule inhibitor, was approved by the us fda for the treatment of metastatic breast cancer in october 2007. Ixempra ixabepilone dosing and administration guide. San diego, ca chemotherapyinduced peripheral neurotoxicity is a major clinical problem representing the doselimiting side effect of many antineoplastic drugs. Ixabepilone is a semisynthetic analog of epothilone b, a natural chemical compound produced by sorangium cellulosum. The calculation of pharmacokinetic pk parameters using a noncompartmental analysis nca approach is required when preparing internal pk study reports and submitting applications to regulatory agencies.
The cytotoxicity of ixabepilone was assessed in vitro in breast, lung, and colon. If a drug has been approved for one use, physicians may elect to use. You might consider the usc pmetrics software pack in r for population modeling, or its bestdose clinical software for maximally precise. Mechanism of action ixempra ixabepilone is a nontaxane microtubuletargeting agent 1 in preclinical studies, ixempra, a semisynthetic analog of epothilone b, had low susceptibility to multiple mechanisms of resistance 1,79. Doses for patients with body surface area bsa greater than 2. Extensively metabolized in the liver, principally by oxidative metabolism via cyp3a4.
Ixabepilone and sunitinib malate in treating patients with. Commercial operations email print friendly share august 17, 2015 08. Ixempra ixabepilone for injection must be constituted with supplied diluent. The pharmacokinetics of ixabepilone were characterized by population pharmacokinetic analysis of data for 16 patients from this trial, who were aged 2 to 18 years median 12 years. To translate promising preclinical data on the combination of vorinostat and ixabepilone for metastatic breast cancer mbc into clinical trials. A phase i clinical, pharmacokinetic, and pharmacodynamic study of weekly or every three week ixabepilone and daily sunitinib in patients with advanced solid tumors alberto j. The recommended dosage of ixempra is 40 mgm 2 administered intravenously over 3 hours every 3 weeks. The degree and type of neuropathy incurred is dependent on the chemotherapeutic drug, dose intensity, and cumulative dose. The pharmacokinetic parameters of ixabepilone in these pediatric patients were compared to the corresponding parameters of adult patients enrolled in clinical. To evaluate the safety and efficacy of ixabepilone as a new antimitotic chemotherapeutic agent for the treatment of breast cancer.
Analysis of pharmacokinetic pk data is concerned with defining the. Ixabepilone was 3fold more potent than docetaxel in the paclitaxelresistant pat21 xenograft model resistant due. Pkquest free pharmacokinetic textbook and software package. The medicinal product ixempra contains the active substance ixabepilone as a singleuse, sterile. Clinical pharmacokinetics science topic explore the latest questions and answers in clinical pharmacokinetics, and find clinical pharmacokinetics experts. To determine the maximum tolerated dose mtd, 37 patients were randomized to schedule a. To determine the recommended phase ii dose of ixabepilone given weekly versus once every three weeks in combination with a fixed dose of sunitinib malate in these patients. Pk solver a free tool to analyse pharmacokinetic data. Preclinical efficacy spectrum and pharmacokinetics of ixabepilone. It is a surprising simple set of data, but still there is enough to play around with. Sigmoidal e max model hill plot of percentage of pbmc with mb and drug concentration. You can also import data from other sources, such as databases or sas files, using the matlab workspace as an intermediate. Data were identified by searches of medline, pubmed, and american society of clinical oncology abstracts from 1966 to march 2008, using the primary search terms ixabepilone, epothilones, bms247550, and breast cancer.
This study extends previous findings regarding the efficacy of ixabepilone and its low susceptibility to tumor resistance mechanisms and describes the pharmacokinetics of this new antineoplastic agent. Ixempra is an anticancer antineoplastic or cytotoxic chemotherapy drug. Ixempra is usually given after other cancer medications have been tried without successful treatment. Phase i trial of ixabepilone administered as three oral.
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