Gleevec®: Pharmacokinetics1,2

• In human adult pharmacokinetic studies, Gleevec was rapidly absorbed after oral dosing; the drug was detected in plasma within 30 minutes of administration.

• Absolute bioavailability was 98%.

• At steady state, the terminal half-lives (t1/2) were approximately 18 and 40 hours for Gleevec and its active metabolite, respectively.

• 81% of Gleevec was eliminated within 7 days.

• Area under the concentration:time curve (AUC) increased with increased dose, and the clearance was approximately 12 to 14 liters per hour.

• Gleevec is metabolized in the liver by the P450 enzyme system, principally CYP3A4. Thus,

coadministration of compounds that inhibit or induce CYP3A4 may affect the clearance of Gleevec.

• Gleevec can alter the metabolism of drugs that are substrates of CYP3A4 and may alter CYP2C9 and CYP2D6 substrates. Therefore, caution is recommended when coadministering CYP3A4, CYP2C9, or CYP2D6 substrates with a narrow therapeutic window.

References

1. Gleevec® (imatinib mesylate) Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2003.

2. Data on file. Novartis Pharmaceuticals Corporation, East Hanover, NJ.