. Pharmacokinetic studies revealed peak serum concentrations of lapatinib 3-6 hours after serum concentrations increased 7 dosing.4 with dose, although high variability is t hen be increased. Lapatinib shows an increase PCI-24781 CRA-02478 over time in the systemic exposure after repeated administration, with serum levels of accumulation of about 2 times t Glicher gift. So after the first dose PK is not a reflection of the chronic levels. The steady state within 6 to 7 days, which reached a half-life of approximately 24 hours. Lapatinib is highly bound to albumin and alpha-1 acid glycoprotein. The volume of distribution of the terminal phase of lapatinib is � 200 L, indicating a distribution of drugs right.
Serum concentrations of lapatinib are characterized by low L Solubility, low permeability t and first-pass metabolism by cytochrome P450 enzymes CYP3A4 and CYP3A5 and to a lesser Ma E by CYP2C19 Descr Nkt A CYP2C8.7 and remains active metabolite against EGFR , but not HER2 0.8 Less than 2% of lapatinib is excreted JNJ 26854165 in the urine. Pharmacokinetic variations of k By drugs may inhibit or induce CYP3A4 or CYP3A5 concomitantly. CYP3A4 / 5 inhibitor should, for example, azoles, antifungal agents, clarithromycin, and grapefruit juice should be avoided. If concomitant use is essential, then the dose reduction to 500 mg of lapatinib once t Resembled properly compensate.3 Conversely, CYP3A4 inducers, such as the ph��nyto Thu, carbamazepine, dexamethasone, St. John, St. John’s will, and serum lapatinib increasing dose decrease may be necessary to maintain the serum level maintained.
Coadministration of lapatinib with other anticancer agents has not VER Changed her Is significant compared to the pharmacokinetic properties of the drug or those adversely alone.9 11 caning of renal function does not require dose adjustment. Hepatic metabolism requires heavy RESTRICTIONS LIMITATION liver function by reducing the dose to be balanced, predicted that the reduction of 1250 mg once-t And 750 mg once resembled t Possible to adjust the AUC in the normal range. However, there are no clinical trials of this dosage dose lapatinib adjustment.3 There is uncertainty about the optimal dose and timing of lapatinib.12 In a phase I evaluation in healthy volunteers, the h HIGHEST dose was 175 mg once daily.
4 In The first phase I trial of dose escalation Lapatinib heavily pretreated cancer patients evaluated, the h HIGHEST dose administered was 1800 mg once-t possible and the lowest with the clinical activity of t was 650 mg once-t possible. Phase I lapatinib monotherapy report response at doses 650-1800 mg, generally 900 to 1200 mg daily.5, 7 lapatinib monotherapy 500 mg twice t Resembled fasting was reported that the same effect and toxicity of t at 1500 mg once daily.13 A challenge, not only with lapatinib, but also with other novel targeted therapies, is the paradigm shift of the maximum tolerated dose to the lowest effective dose. Targeted therapies, which by its nature it is a goal, not associated with systemic side effects limit the dose with Herk Observed mmlichen cytotoxic chemotherapeutic agents. Administered as such can kill maximum doses in early studies of the extent of the required dose for efficacy. Although the maximum tolerated Possible dose may be administered or reported, the clinical utility of this information is low. The installation of alternative settings for targeted agents in phase I clinical trial design, such as PHA