Pharmacokinetics of the 5HT3 receptor antagonist tropisetron in children.
A pharmacokinetic study in children was performed to assess whether the pharmacokinetic profile of tropisetron in pediatric patients in similar to that in adults. In three pediatric centers, three dosages were tested in two age groups during chemotherapy (Group A, 3-6 years, 2, 5, or 20 mg/m2; group B, 7-15 years, 2, 5, or 20 mg). Children received tropisetron intravenously (course 1) or orally (course 2) before the start of chemotherapy. Blood samples were drawn over 24 hours. Tropisetron treatment continued for up to 6 days at the same daily dose, administered orally. Data were available for 45 patients after intravenous and for 38 patients after oral administration. 82% of course 1 patients and 72% of course 2 patients had no emesis on day 1. Headache occurred in eight patients and abdominal symptoms in three patients. Terminal half-life (5.3-6.6 hours), tmax (1.4-1.5 hours), and absolute bioavailability (41-42%) were identical in both age groups and comparable to those in adults. Because of a smaller volume of distribution, group A children showed a higher Cmax/dose (P < .001) and a higher area under curve (AUC) dose (P < .05) than adults. All parameters were independent of the dose administered. In conclusion, the elimination and absolute bioavailability of tropisetron in children are similar to those in adults. Because of its age-dependent volume of distribution, tropisetron should be administered once a day according to the body surface area in children below 10 years of age.
Gaedicke
G
G
Department of Pediatrics, Charité University Hospital, Berlin, Germany.
Erttmann
R
R
Henze
G
G
Hartmann
W
W
Drechsler
S
S
Grass
P
P
Faerber
L
L
Kutz
K
K
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000009:adverse effects; D019540:Area Under Curve; D001682:Biological Availability; D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006207:Half-Life; D006261:Headache / Q000209:etiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D011446:Prospective Studies; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D012449:Safety; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D016896:Treatment Outcome; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D000077526:Tropisetron