Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy.
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.
Gurpide
Alfonso
A
Oncology Department, Clínica Universitaria de Navarra, University of Navarra, Navarra, Spain. agurpide@unav.es
Sadaba
Belen
B
Martin-Algarra
Salvador
S
Azanza
Jose R
JR
Lopez-Picazo
Jose M
JM
Campanero
Miguel A
MA
Cabello
Juan P
JP
Gil-Aldea
Isabel
I
de la Cruz
Susana
S
Fernandez Gallego
Victor
V
Reyna
Carmen
C
Olier Garate
Clara
C
Blanco-Prieto
María J
MJ
Ceballos
Jaime
J
Garcia-Foncillas
Jesus
J
Perez-Gracia
Jose L
JL
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
D000932:Antiemetics; D000970:Antineoplastic Agents; D017829:Granisetron; D017671:Platinum Compounds