Effects of food on the pharmacokinetics of ponatinib in healthy subjects.
What is known and objective Ponatinib is a potent oral tyrosine kinase inhibitor with activity against BCR- ABL, the primary driver of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. This single-centre, single-dose, randomized, open-label, three-period c...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 38; no. 6; pp. 440 - 445 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104150456&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104150456 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2013 vid: 38 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104150456 91673869 10.1111/jcpt.12082 NLM23888935 104150456 ppf: 440 ppct: 5 formats: fmt: @attributes: type: P tig: atl: Effects of food on the pharmacokinetics of ponatinib in healthy subjects. aug: au: Narasimhan, N. I. Dorer, D. J. Niland, K. Haluska, F. Sonnichsen, Daryl affil: ARIAD Pharmaceuticals, Inc. sug: subj: Protein Kinases Antagonists and Inhibitors Antineoplastic Agents Administration and Dosage Antineoplastic Agents Pharmacokinetics Drug-Food Interactions Leukemia Drug Therapy Human Randomized Controlled Trials Crossover Design Biological Availability Descriptive Statistics Analysis of Variance Antineoplastic Agents Blood Time Factors Chromatography, Liquid Methods Mass Spectrometry Methods Confidence Intervals Data Analysis Software Wilcoxon Signed Rank Test Adult Middle Age Male Female Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: What is known and objective Ponatinib is a potent oral tyrosine kinase inhibitor with activity against BCR- ABL, the primary driver of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. This single-centre, single-dose, randomized, open-label, three-period crossover study evaluated the pharmacokinetics and bioavailability of a single oral dose of ponatinib (45-mg tablet) under fasting conditions and following consumption of high- and low-fat meals by healthy subjects. Methods Subjects were randomly assigned to one of the six possible treatment sequences, each evaluating three ponatinib 45-mg treatments: administered under fasting conditions; administered after a high-fat meal; or administered after a standardized low-fat meal. The high-fat meal derived approximately 50% of its total caloric content from fat, with approximately 150, 250 and 500-600 calories derived from protein, carbohydrates and fat, respectively (total of approximately 900-1000 calories). The standardized low-fat meal derived no more than 20% of total caloric content from fat, with approximately 56, 428 and 63 calories derived from protein, carbohydrates and fat, respectively (total of approximately 547 calories). During each of the three treatment periods, blood samples were collected predose and at 13 time points over the 96-h post-dose interval. Plasma concentrations of ponatinib were measured by liquid chromatography/tandem mass spectrometry. Mixed-model analyses of variance ( anova) were performed on natural log-transformed PK parameters Cmax and AUC0-∞. Results and discussion Geometric mean maximum plasma concentration ( Cmax) values for the fasted, low-fat and high-fat regimens were 54·7, 51·6 and 51·5 ng/mL, respectively. Geometric mean area under the concentration-time curve from time zero to infinity (AUC0-∞) values for the fasted, low-fat and high-fat regimens were 1273, 1244 and 1392 h × ng/mL, respectively. All limits of the 90% CIs of the estimated geometric mean ratios for Cmax and all AUC comparisons fell within the 80%-125% margins. These results indicate that consumption of a high- or low-fat meal within 30 min prior to administration of ponatinib had no effect on the single-dose pharmacokinetics of ponatinib. What is new and conclusion Food does not affect the single-dose pharmacokinetics of ponatinib. These data demonstrate that ponatinib may be administered with or without food. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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