title: Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy.
abstract: BACKGROUND
  5-HT3-receptor antagonists are one of the mainstays of antiemetic treatment, and they are administered either i.v. or orally. Nevertheless, sometimes neither administration route is feasible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to evaluate the bioavailability of s.c. granisetron.
  
  
  METHODS
  Patients receiving platinum-based chemotherapy were randomized to receive 3 mg of granisetron either s.c. or i.v. in a crossover manner during two cycles. Blood and urine samples were collected after each cycle. Pharmacokinetic parameters observed with each administration route were compared by analysis of variance.
  
  
  RESULTS
  From May to November 2005, 31 patients were included and 25 were evaluable. Subcutaneous granisetron resulted in a 27% higher area under the concentration-time curve for 0-12 hours (AUC(0-12h)) and higher levels at 12 hours, with similar values for AUC(0-24h). The maximum concentration was lower with the s.c. than with the i.v. route and was observed 30 minutes following s.c. administration.
  
  
  CONCLUSIONS
  Granisetron administered s.c. achieves complete bioavailability. This is the first study that shows that s.c. granisetron might be a valid alternative to i.v. delivery. Further trials to confirm clinical equivalence are warranted. This new route of administration might be especially relevant for outpatient management of emesis in cancer patients.
authors.affiliation: Oncology Department, Clínica Universitaria de Navarra, University of Navarra, Navarra, Spain. agurpide@unav.es
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gurpide
authors.forename: Belen
authors.initials: B
authors.lastname: Sadaba
authors.forename: Salvador
authors.initials: S
authors.lastname: Martin-Algarra
authors.forename: Jose R
authors.initials: JR
authors.lastname: Azanza
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lopez-Picazo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Campanero
authors.forename: Juan P
authors.initials: JP
authors.lastname: Cabello
authors.forename: Isabel
authors.initials: I
authors.lastname: Gil-Aldea
authors.forename: Susana
authors.initials: S
authors.lastname: de la Cruz
authors.forename: Victor
authors.initials: V
authors.lastname: Fernandez Gallego
authors.forename: Carmen
authors.initials: C
authors.lastname: Reyna
authors.forename: Clara
authors.initials: C
authors.lastname: Olier Garate
authors.forename: María J
authors.initials: MJ
authors.lastname: Blanco-Prieto
authors.forename: Jaime
authors.initials: J
authors.lastname: Ceballos
authors.forename: Jesus
authors.initials: J
authors.lastname: Garcia-Foncillas
authors.forename: Jose L
authors.initials: JL
authors.lastname: Perez-Gracia
mesh_terms: D000284:Administration, Oral; D000932:Antiemetics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D001682:Biological Availability; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018592:Cross-Over Studies; D005260:Female; D005500:Follow-Up Studies; D017829:Granisetron / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000009:adverse effects*; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D017829:Granisetron; D017671:Platinum Compounds