Pharmacokinetics of granisetron in adults and children with malignant diseases.
Granisetron (GRN) is widely used for patients with various cancers who suffer from chemotherapy-induced vomiting and nausea. The, pharmacokinetics of GRN has not been fully evaluated in such patients, however, and its dosage regimen is still controversial. In this study, we determined GRN levels in serum and urine from lung cancer patients and children suffering from cancer after intravenous infusion. In lung cancer patients, the interindividual variations in t(1/2beta), area under the concentration-time curve (AUC), and Vd(beta) were relatively smaller than expected from previous reports on healthy subjects, while t(1/2beta) was prolonged more than 5-fold in healthy subjects. Urinary excretion of unchanged GRN in lung cancer patients was ca. 15% of dose, consistent with previous reports, and one individual demonstrated an even higher urinary excretion (ca. 45%). The pharmacokinetic parameters of GRN in child cancer patients varied markedly among individuals, and some child patients had smaller t(1/2beta) than adult patients. In these cases, GRN should be administered at shorter intervals. These results suggested that a pharmacokinetic study of GRN was necessary for planning a dosage regimen and managing chemotherapy-induced vomiting and nausea.
Wada
I
I
Hokkaido University Dental Hospital, Sapporo, Japan. iwada@den.hokudai.ac.jp
Takeda
T
T
Sato
M
M
Saitoh
H
H
Nakabayashi
T
T
Mino
K
K
Honma
T
T
Takada
M
M
Hirano
K
K
D000293:Adolescent; D000368:Aged; D000375:Aging / Q000378:metabolism; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000009:adverse effects; D019540:Area Under Curve; D002648:Child; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008111:Liver Function Tests; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000378:metabolism*
D000932:Antiemetics; D000970:Antineoplastic Agents; D017829:Granisetron