Evaluation of the exposure equivalence of oral versus intravenous temozolomide

• Published in: Cancer chemotherapy and pharmacology Vol. 65; no. 4; pp. 727 - 734
• Main Authors: Diez, Blanca D, Statkevich, Paul, Zhu, Yali, Abutarif, Malaz A, Xuan, Fengjuan, Kantesaria, Bhavna, Cutler, David, Cantillon, Marc, Schwarz, Max, Pallotta, Maria Guadalupe, Ottaviano, Fabio H
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.03.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Administration, Oral; Adult; Anemia - chemically induced; Antineoplastic agents; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Agents, Alkylating - pharmacokinetics; Area Under Curve; Biological and medical sciences; Cancer Research; central nervous system; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - metabolism; confidence interval; Constipation - chemically induced; Cross-Over Studies; Dacarbazine - administration & dosage; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacokinetics; Drug Administration Schedule; drugs; Female; glioma; Headache - chemically induced; Humans; Infusions, Intravenous; injection site; intravenous injection; lymphoma; Male; Medical sciences; Medicine; Medicine & Public Health; melanoma; Metabolic Clearance Rate; Middle Aged; Nausea - chemically induced; Oncology; oral administration; Original; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Therapeutic Equivalency; Time Factors; Vomiting - chemically induced; Temozolomide; Oral; Pharmacokinetics; Intravenous; Exposure equivalence; AUC; Antineoplastic agent; Evaluation; Intravenous administration; Oral administration; Exposure; Alkylating agent; Equivalence; Comparative study
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-009-1078-6

Purpose 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/m² of oral temozolomide on days 1, 2 and 5. On days 3 and 4, subjects received 150 mg/m² 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.