title: Higher capecitabine AUC in elderly patients with advanced colorectal cancer (SWOGS0030).
abstract: BACKGROUND
  The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ≥70 years and <60 years were compared in SWOG0030.
  
  
  METHODS
  Twenty-nine unresectable colorectal cancer patients were stratified to either ≥70 or <60 years of age, where the disposition of capecitabine and its metabolites were compared.
  
  
  RESULTS
  Notable increase in capecitabine area under the curve (AUC) was accompanied by reduction in capecitabine clearance in ≥70 years patients (P<0.05). No difference in 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5FU) AUCs between the two age groups, suggesting that carboxylesterase and cytidine deaminase (CDA) activity was similar between the two age groups. These results suggest that metabolic enzymes involved in converting capecitabine metabolites are not altered by age. An elevation in capecitabine Cmax and reduction in clearance was seen in females, where capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC (46%) (P<0.05) was also noted, suggesting that CDA activity may be higher in females.
  
  
  CONCLUSIONS
  Increases in capecitabine Cmax and AUC was observed in patients ≥70 years when compared with younger patients who were >60 years.
authors.affiliation: 1] Department of Pharmacy, University of Southern California, Los Angeles, CA, USA [2] Department of Oncology, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Louie
authors.forename: B
authors.initials: B
authors.lastname: Ely
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
authors.forename: K S
authors.initials: KS
authors.lastname: Albain
authors.forename: C
authors.initials: C
authors.lastname: Gotay
authors.forename: D
authors.initials: D
authors.lastname: Coleman
authors.forename: D
authors.initials: D
authors.lastname: Raghavan
authors.forename: A F
authors.initials: AF
authors.lastname: Shields
authors.forename: P J
authors.initials: PJ
authors.lastname: Gold
authors.forename: C D
authors.initials: CD
authors.lastname: Blanke
mesh_terms: D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005467:Floxuridine / Q000097:blood; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012737:Sex Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; D000069287:Capecitabine; C418208:5'-deoxy-5-fluorocytidine; D005472:Fluorouracil; C025034:doxifluridine
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