Pkquest free pharmacokinetic textbook and software package. The ixabepilone concentration in constituted solution is 2 mgml. The r project for statistical computing getting started. The recommended dosage of ixempra is 40 mgm 2 administered intravenously over 3 hours every 3 weeks. R is a free software environment for statistical computing and graphics. 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. Ixempra may also be used for purposes not listed in this medication guide. Ixabepilone was 3fold more potent than docetaxel in the paclitaxelresistant pat21 xenograft model resistant due. The medicinal product ixempra contains the active substance ixabepilone as a singleuse, sterile. Ixabepilone demonstrated potent cytotoxicity in a broad range of human cancer cell lines in vitro and in a wide range of xenografts in vivo. Ixempra is usually given after other cancer medications have been tried without successful treatment. The bioavailability of ixabepilone in this oral formulation from study ca163088 was 43%, with cmax 50. Ixabepilone was designed through medicinal chemistry to improve upon these properties pharmacology.
Ixabepilone and carboplatin for hormone receptor positiveher2. Im now working with a mixed model lme in r software. Commercial operations email print friendly share august 17, 2015 08. Ixempra definition of ixempra by medical dictionary. In this post i want to analyze a first order pharmocokinetcs problem. Pkstamp pharmacokinetic sampling times allocation matlab platform is a library compiled as a single executable file, which does not. Looking for pharmacokinetics software researchgate. The pharmacokinetic profile of ixabepilone in adults was. R pharm acquires ixempra r ixabepilone from bristolmyers squibb and launches u.
Ixempra binds directly to betatubulin subunits and suppresses their dynamic instability, blocking the mitotic phase of the cell division cycle and inducing cell. Choice of environment, language, or package is generally dependent on tools availability, cost, ease of use, and expertise. If a drug has been approved for one use, physicians may elect to use. Ixempra ixabepilone dosing and administration guide. 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. Dose reduction is required in certain patients with elevated ast, alt, or bilirubin 2. The pknca r package is designed to perform all noncompartmental analysis nca calculations for pharmacokinetic pk data. 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. Ixempra ixabepilone is used to treat advanced breast cancer. Which is the best package for analysis of pharmacokinetic.
You might consider the usc pmetrics software pack in r for population modeling, or its bestdose clinical software for maximally precise. Preclinical efficacy spectrum and pharmacokinetics of. We conducted a randomized twoarm phase ib clinical trial of ascending doses of vorinostat and ixabepilone in prior treated mbc patients. San diego, ca chemotherapyinduced peripheral neurotoxicity is a major clinical problem representing the doselimiting side effect of many antineoplastic drugs.
Ixempra ixabepilone for injection must be constituted with supplied diluent. Which pk pharmacokinetic software is most widely used by. 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 phase iii and pharmacokinetic trial of ixabepilone was conducted in. Splus, r is considered for performing pre and postprocessing, where nonmem software handles the analyses portion. Ixempra pharmacokinetics absorption bioavailability. 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 evaluate the pharmacokinetic profiles of the combination of ixabepilone and sunitinib malate and correlate them with activity andor toxicity. To determine the maximum tolerated dose mtd, 37 patients were randomized to schedule a. The pharmacokinetic profile of ixabepilone was established in mice and humans. It compiles and runs on a wide variety of unix platforms, windows and macos. It is a surprising simple set of data, but still there is enough to play around with.
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. User friendly pk and graphical software with built in physiologically based pharmacokinetic, deconvolution, noncompartment pk and much more. Trent1, pasquale benedetto1, caio rochalima1, and jaime r. A phase i clinical, pharmacokinetic, and pharmacodynamic study. Each specific drug example saved as excel file that can be used as template for your own. A phase i clinical, pharmacokinetic, and pharmacodynamic. Methods and software tools for design evaluation in. Extensively metabolized in the liver, principally by oxidative metabolism via cyp3a4. Ixempra is an anticancer antineoplastic or cytotoxic chemotherapy drug. 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. The final solution must be used within 6 hours of preparation. 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. Sigmoidal e max model hill plot of percentage of pbmc with mb and drug concentration.
The recommended dose of ixempra is 40 mgm2 infused intravenously over 3 hours every 3 weeks 2. Ixabepilone auc and c max also showed correlations r 2 0. Pharmacokinetics of ixabepilone was investigated in rat, mouse and dog, species used in toxicology. Pk solver a free tool to analyse pharmacokinetic data. To evaluate the safety and efficacy of ixabepilone as a new antimitotic chemotherapeutic agent for the treatment of breast cancer. The degree and type of neuropathy incurred is dependent on the chemotherapeutic drug, dose intensity, and cumulative dose. Read 36 answers by scientists with 20 recommendations from their colleagues to the question asked by roland j. 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. To translate promising preclinical data on the combination of vorinostat and ixabepilone for metastatic breast cancer mbc into clinical trials. Doses for patients with body surface area bsa greater than 2. Phase i trial and pharmacokinetic study of ixabepilone. Epothilone b itself could not be developed as a pharmaceutical drug because of poor metabolic stability and pharmacokinetics. Phase ib trial of ixabepilone and vorinostat in metastatic. Ixabepilone is an epothilone, a novel class of nontaxane microtubule stabilizing agents.
Montero1, deukwoo kwon2, aurea flores1, krisztina kovacs1, jonathan c. Preclinical efficacy spectrum and pharmacokinetics of ixabepilone. Ixempra is classified as an antimicrotubule agent or an epothilone b analog. Adult patients received ixabepilone as a 1h infusion daily for 5 days every 3 weeks.
To determine the recommended phase ii dose of combination ixabepilone plus carboplatin based on the maximum tolerated dose, pharmacokinetics, optimum schedule, and safety. Bristolmyers squibb, a cytotoxic microtubule inhibitor, was approved by the us fda for the treatment of metastatic breast cancer in october 2007. 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. 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. A graphical user interface gui package using the r software pfim interface is also available but does not include recent methodological developments. Constituted solution must be diluted with lactated ringers injection, usp, to a final ixabepilone concentration of 0. Ixabepilone and sunitinib malate in treating patients with. This video will show steps for calculation of pk parameters using r. Clinical pharmacokinetics science topic explore the latest questions and answers in clinical pharmacokinetics, and find clinical pharmacokinetics experts. A phase iii trial and pharmacokinetic study of ixabepilone in adult. 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 pharmacokinetic parameters of ixabepilone in these pediatric patients were compared to the corresponding parameters of adult patients enrolled in clinical. 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.
A simple but easytouse menudriven package created for data analysis of ivivc. The cytotoxicity of ixabepilone was assessed in vitro in breast, lung, and colon. A phase i and pharmacokinetic study of ixabepilone in. Analysis of pharmacokinetic pk data is concerned with defining the. Not known if ixabepilone is distributed into human milk. Ixabepilone is a semisynthetic analog of epothilone b, a natural chemical compound produced by sorangium cellulosum. You can also import data from other sources, such as databases or sas files, using the matlab workspace as an intermediate. Phase i trial of ixabepilone administered as three oral. Ixempra can be used alone or with another cancer medicine called xeloda capecitabine.
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