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Reduced exposure of imatinib after coadministration with acetaminophen in mice.

Nassar I, Pasupati T, Judson JP, Segarra I - Indian J Pharmacol (2009)

Bottom Line: It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated.Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours).The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur, Malaysia.

ABSTRACT

Purpose: Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen.

Materials and methods: Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC.

Results: Imatinib AUC(0-12) was 27.04 +/- 0.38 mg.h/ml, C(max) was 7.21 +/- 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours).

Conclusions: The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.

No MeSH data available.


Related in: MedlinePlus

Plasma concentration-time curve profile of imatinib after oral administration to mice
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Figure 0002: Plasma concentration-time curve profile of imatinib after oral administration to mice

Mentions: The pharmacokinetic profile of imatinib in plasma after oral administration is shown in Figure 2 and the pharmacokinetic parameters calculated using non-compartmental techniques are listed in Table 1. Mice treated with 100 mg/kg imatinib PO showed a rapid increase in imatinib plasma concentration to reach the Cmax (7.21 ± 0.99 μg/ml) at 2 hours (Tmax). Following the Tmax, the imatinib plasma concentration declined gradually with an elimination half-life of 2.3 hours. The total imatinib exposure or AUC0-∞ was determined to be 27.61 μg h/ ml, Cl/F was calculated to be 3.7 l/h/kg, and the MRT was 3.3 hours.


Reduced exposure of imatinib after coadministration with acetaminophen in mice.

Nassar I, Pasupati T, Judson JP, Segarra I - Indian J Pharmacol (2009)

Plasma concentration-time curve profile of imatinib after oral administration to mice
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875735&req=5

Figure 0002: Plasma concentration-time curve profile of imatinib after oral administration to mice
Mentions: The pharmacokinetic profile of imatinib in plasma after oral administration is shown in Figure 2 and the pharmacokinetic parameters calculated using non-compartmental techniques are listed in Table 1. Mice treated with 100 mg/kg imatinib PO showed a rapid increase in imatinib plasma concentration to reach the Cmax (7.21 ± 0.99 μg/ml) at 2 hours (Tmax). Following the Tmax, the imatinib plasma concentration declined gradually with an elimination half-life of 2.3 hours. The total imatinib exposure or AUC0-∞ was determined to be 27.61 μg h/ ml, Cl/F was calculated to be 3.7 l/h/kg, and the MRT was 3.3 hours.

Bottom Line: It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated.Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours).The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur, Malaysia.

ABSTRACT

Purpose: Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen.

Materials and methods: Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC.

Results: Imatinib AUC(0-12) was 27.04 +/- 0.38 mg.h/ml, C(max) was 7.21 +/- 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours).

Conclusions: The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.

No MeSH data available.


Related in: MedlinePlus