Several clinical trials have demonstrated that the three-drug combination of @entity901 , @entity1487 ( @entity1487 ) and @entity4181 (LV) administered chronomodulated improved antitumour efficacy in the treatment of metastatic @entity14 and was better tolerated than constant-rate infusion. However, only a few pharmacokinetic data of @entity1487 during chronomodulated infusion are available but up to now not for @entity901 . In this pilot study, the @entity902 levels of plasma ultrafiltrate (PUF) and total plasma were monitored during chronomodulated infusion of @entity901 , @entity1487 and LV in 7 @entity1 with metastatic @entity1820 . A cycle of the 4-day chemotherapeutic regimen consisted of 12-h infusions with sinusoidal drug delivery rate of: @entity901 (25 mg/m2/d, peak at 16:00 hours), @entity1487 and LV (750 mg/m2/d and 150 mg/m2/d, respectively, peak at 4:00 hours), the same scheme was reinitiated on day 15. Blood samples were collected on day 1 and day 4 during different cycles. Concentration-time profiles of ultrafilterable and total @entity902 in plasma during chronomodulated infusion were characterised. As expected, we found residual @entity902 levels in total plasma but not in PUF prior next cycle. Comparing day 1 with day 4, Cmax of @entity902 in PUF was significantly increased (84 +/- 13 ng/ml vs. 131 +/- 22 ng/ml, P = 0.012) as well as AUC0-24h of @entity902 in PUF (0.97 +/- 0.29 microg x h/ml vs. 1.90 +/- 0.44 microg x h/ml, P = 0.018). The same effect was observed for total plasma @entity902 suggesting an accumulation within the cycle. The observed interindividual variability of Cmax, tmax, AUC0-24h, t1/2 was moderate. Because of the small sample size in this pilot investigation, the findings need to be confirmed in larger pharmacokinetic studies. In a next step individual pharmacokinetic parameters should be associated with @entity1 specific parameters and treatment-induced @entity137 .

Pharmacokinetics of XXXX during chronomodulated infusion in metastatic @entity1820 @entity1 : a pilot investigation with preliminary results.

@entity901 :: ('MESH:C030110', 'Chemical') :: ['oxaliplatin'] @entity4181 :: ('MESH:D002955', 'Chemical') :: ['leucovorin'] @entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity1820 :: ('MESH:D005770', 'Disease') :: ['gastrointestinal cancer'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5-FU', '5-fluorouracil']
@entity901 :: (MESH:C030110,Chemical) :: ['oxaliplatin']
