Evaluation of the exposure equivalence of oral versus intravenous temozolomide.
OBJECTIVE
Oral temozolomide is approved in many countries for malignant glioma and for melanoma in some countries outside the USA. This study evaluated the exposure equivalence and safety of temozolomide by intravenous infusion and oral administration.


METHODS
Subjects with primary central nervous system malignancies (excluding central nervous system lymphoma) received 200 mg/m(2) of oral temozolomide on days 1, 2 and 5. On days 3 and 4, subjects received 150 mg/m(2) temozolomide either as a 90-min intravenous infusion on one day or by oral administration on an alternate day.


RESULTS
Ratio of log-transformed means (intravenous:oral) of area under the concentration-time curve and maximum concentration of drug after dosing for temozolomide and 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) met exposure equivalence criteria (90% confidence interval = 0.8-1.25). Treatment-emergent adverse events were consistent with those reported previously in subjects with recurrent glioma treated with oral temozolomide, except for mostly mild and transient injection site reactions with intravenous administration.


CONCLUSIONS
This study demonstrated an exposure equivalence of a 90-min intravenous infusion of temozolomide and an equivalent oral dose.
Diez
Blanca D
BD
Department of Neuro-Oncology, Institute of Neurological Research Dr Raul Carrea (FLENI), Montañeses 2325, Buenos Aires 1428, Argentina. bdiez@fleni.org.ar
Statkevich
Paul
P
Zhu
Yali
Y
Abutarif
Malaz A
MA
Xuan
Fengjuan
F
Kantesaria
Bhavna
B
Cutler
David
D
Cantillon
Marc
M
Schwarz
Max
M
Pallotta
Maria Guadalupe
MG
Ottaviano
Fabio H
FH
D000284:Administration, Oral; D000328:Adult; D000740:Anemia / Q000139:chemically induced; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003248:Constipation / Q000139:chemically induced; D018592:Cross-Over Studies; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D000077204:Temozolomide; D013810:Therapeutic Equivalency; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide