The relationships between the administered dose, clearance, and the @entity137 spectrum of @entity1487 ( @entity1487 ) administered as 72-hour constant infusion have been studied in 21 @entity1 with @entity5 . This was done as a pilot study for possible future combination using @entity1487 as a radiosensitizer. Individual @entity1 tolerated up to 65 mg/kg/24 hours, but serious @entity137 appeared once as low as 35 mg/kg. Limiting @entity137 proved to be "mixed" with @entity1944 ( @entity390 and @entity391 ), @entity3136 , and central nervous system signs all occurring in various @entity1 . Central nervous system effects (both @entity76 ) proved as troublesome as @entity3136 . There was only a general link between the administered dose and the subsequent @entity137 grade, but a reasonably quantitative relationship emerged when the serum @entity1487 levels obtained and the degree of @entity1 @entity137 were compared. The clearance of @entity1487 was confirmed to be nonlinear over the entire dose range studied (25-65 mg/kg/24 hours), consistent with a two-compartment model of drug metabolism. One compartment appears to be @entity99 (probably anabolic removal) which is saturated at just below 15 mg/kg/day. Doses above that level lead to drug accumulation. No steady state was reached, contrary to previous reports. At the higher infusion rates, clearance progressively approaches that predicted by the assumption that the second compartment is splanchnic blood flow and catabolism. While @entity1487 can be administered as a 72-hour infusion as one possible schedule for use as a single agent or for combined modality studies, CNS effects are quite troublesome in comparison to longer infusions to @entity137 .

Phase I and pharmacologic study of 72-hour infused XXXX in @entity1 .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity1944 :: ('MESH:D007410', 'Disease') :: ['upper intestinal symptoms'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity3136 :: ('MESH:D013280', 'Disease') :: ['stomatitis'] @entity5 :: ('MESH:D009369', 'Disease') :: ['advanced cancer'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity76 :: ('MESH:D002526', 'Disease') :: ['cerebellar and vomiting'] @entity99 :: ('MESH:D056486', 'Disease') :: ['systemic (extra-hepatic) metabolism'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5-FU', '5-Fu', '5-fluorouracil']
@entity1487 :: (MESH:D005472,Chemical) :: ['5-fluorouracil']
