Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose

Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases involved in chronic myelogenous leukemia and gastrointestinal stromal tumors. Mice were given imatinib PO (50 mg/kg) or IV (12.5 mg/kg) and plasma, liver, brain, spleen, kidney disposition profiles analyzed. Plasma t1/2 was 4.5 h. IV plasma AUC0→∞ w...

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Autores principales: Teoh, Magdalene, Radhakrishnan, Shantini, Moo, Kai S., Narayanan, Prasad, Bukhari, Nadeem I., Segarra, Ignacio
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Farmacia
Leucemia Mieloide
bioavailability; chronic myeloid leukemia; gastrointestinal stromal tumor; imatinib; pharmacokinetics;tissue distribution
Farmacocinética
Distribución Tisular
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/7928
http://www.latamjpharm.org/resumenes/29/3/LAJOP_29_3_1_15.pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-7928
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Farmacia
Leucemia Mieloide
bioavailability; chronic myeloid leukemia; gastrointestinal stromal tumor; imatinib; pharmacokinetics;tissue distribution
Farmacocinética
Distribución Tisular
spellingShingle Farmacia
Leucemia Mieloide
bioavailability; chronic myeloid leukemia; gastrointestinal stromal tumor; imatinib; pharmacokinetics;tissue distribution
Farmacocinética
Distribución Tisular
Teoh, Magdalene
Radhakrishnan, Shantini
Moo, Kai S.
Narayanan, Prasad
Bukhari, Nadeem I.
Segarra, Ignacio
Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
topic_facet Farmacia
Leucemia Mieloide
bioavailability; chronic myeloid leukemia; gastrointestinal stromal tumor; imatinib; pharmacokinetics;tissue distribution
Farmacocinética
Distribución Tisular
description Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases involved in chronic myelogenous leukemia and gastrointestinal stromal tumors. Mice were given imatinib PO (50 mg/kg) or IV (12.5 mg/kg) and plasma, liver, brain, spleen, kidney disposition profiles analyzed. Plasma t1/2 was 4.5 h. IV plasma AUC0→∞ was 11.59 μg·h/mL, MRT was 4.87 h, Cl was 1.08 l/h/kg and VSS was 5.23 l/kg. PO AUC0→∞ was 12.82 μg·h/mL, MRT 5.1 h, CMAX was 6.99 ± 2.84 μg/mL, absorption rate constant, Ka was 4.348 h–1, bioavailability was 27.7%, VSS was 5.51 l/kg. The hepatic extraction ratio was 0.384 and the minimum dose fraction absorbed was 0.450. IV AUC0→∞ tissue-to-plasma ratios were 2.59 (spleen, kidney) and 2.91 (liver) but increased after PO administration in spleen (3.68) and kidney (3.49) and decreased in liver (2.75). Liver and kidney correlations with plasma concentrations suggests perfusion-limited uptake. Spleen counter-clockwise profile suggests non-concentration dependent uptake. Brain penetration was minimal.
format Articulo
Articulo
author Teoh, Magdalene
Radhakrishnan, Shantini
Moo, Kai S.
Narayanan, Prasad
Bukhari, Nadeem I.
Segarra, Ignacio
author_facet Teoh, Magdalene
Radhakrishnan, Shantini
Moo, Kai S.
Narayanan, Prasad
Bukhari, Nadeem I.
Segarra, Ignacio
author_sort Teoh, Magdalene
title Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
title_short Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
title_full Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
title_fullStr Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
title_full_unstemmed Pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
title_sort pharmacokinetics, tissue distribution and bioavailability of imatinib in mice after administration of a single oral and an intravenous bolus dose
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/7928
http://www.latamjpharm.org/resumenes/29/3/LAJOP_29_3_1_15.pdf
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