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Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients.

ABSTRACT: BACKGROUND:Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultaneous intake of up to four capsules or tablets each 100 mg. A new 400 mg film coated tablet developed due to the need to swallow multiple capsules or tablets per dose and that was a negative impact on treatment adherence. SUBJECTS AND METHODS:A group of 36 patients were randomly assigned to receive Imatinib as 4×100 mg capsules, 4×100 mg tablets and 1×400 mg tablet. Blood sampling was performed for up to 48 h after first dosing. After that, subjects were monitored to assess drug related adverse events. Pharmacokinetic parameters were assessed using concentration-time curves for plasma Imatinib and its metabolite. RESULTS:Mean area under the curve (AUC (0-?)) values were 27011, 25811 and 25699 ng/ml for 4×100 mg capsules, 4×100 mg tablets and 1×400 mg tablets, respectively. Cmax values were 1548, 1605 and 1622 ng/ml and t1/2 values were 15.7, 15.8 and 15.6 h. The Test/Reference ratios for AUC (0-?), AUC (0-48), and Cmax were 0.99, 0.99 and 1.02 for 4×100 mg tablets versus 4×100 mg capsules and 0.96, 0.96 and 0.99 for 1×400 mg tablet versus 4×100 mg capsules. The 95% confidence intervals were fully contained within the accepted interval. The mild and moderate adverse events considered to be drug related were reported. These events showed no clustering by type of dosage form and were of little to no clinical significance. CONCLUSION:Film coated (400 mg) tablet dosage formulations of Imatinib is bioequivalent to the commercial available 100 mg hard gelatin capsule, and is as safe and well tolerated.

SUBMITTER: Mohajeri E

PROVIDER: S-EPMC4748686 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients.

Mohajeri Ehsan E Kalantari-Khandani Behjat B Pardakhty Abbas A Safavi Moeinadin M Ansari Mehdi M

International journal of hematology-oncology and stem cell research 20151001 4

<h4>Background</h4>Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultaneous intake of up to four capsules or tablets each 100 mg. A new 400 mg film coated tablet developed due to the need to swallow multiple capsules or tablets per dose and that was a negative impact on treatment adherence.<h4>Subjects and methods</h4>A group of 36 patients were randomly assigned to receive Imatinib as 4×100 m ...[more]

PMID: 26865926

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Project description:Background and objectiveA novel tiotropium bromide monodose capsule dry powder inhaler (DPI) formulation and device have been developed. The formulation was based on a spray-dried matrix that enhances the aerosolizaton properties, allowing a less active tiotropium metered dose (13 µg/capsule) while maintaining the same delivered dose (10 µg/actuation). This study describes the pharmacokinetic bioequivalence to the reference product.MethodsThis randomized, two-stage, crossover, semi-replicate (three-way) study was performed in healthy volunteers. In each study period, subjects received a single dose of two capsules (20 μg delivered dose) of the study medication, separated by a 14-day washout period: tiotropium 10 μg delivered dose (Laboratorios Liconsa, Spain) and Spiriva HandiHaler(®) (Boehringer Ingelheim Pharma GmbH & Co KG, Germany). Blood samples were obtained up to 48 h post-dose to evaluate the comparative bioavailability. Tiotropium was measured in plasma by means of dual stage liquid-liquid extraction followed by the two-dimensional ultra-high performance liquid chromatography sensitive sub-pg/mL bioanalytical method. The main pharmacokinetic parameters were maximum plasma concentration (C max), area under the concentration-time curve (AUC) from time zero hours to the last observed concentration at time t (AUC t ), and AUC from time zero hours to 30 min (AUC0.5). Bioequivalence was accepted if the 90.20 % confidence interval (CI) for the ratio test/reference of the primary pharmacokinetic parameters lay within the acceptance range of 80-125 %. Safety assessment was a secondary endpoint.ResultsA total of 30 subjects were randomized and bioequivalence was demonstrated for all primary pharmacokinetic parameters: C max (CI 87.26-106.60 %), AUC t (CI 101.33-111.64 %), and AUC0.5 (CI 97.95-113.49 %). Both study treatments were well tolerated (four non-serious adverse events [AEs] were reported in four subjects: one AE before any product administration, two AEs after test product administration; and one AE after reference product administration).ConclusionsBoth products containing tiotropium 10 µg delivered-dose DPI were bioequivalent and showed good tolerability and a similar safety profile.

Dataset Information

Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients.

Publications

Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients.

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