Pharmacokinetics of Temozolomide in a Patient With Glioblastoma Undergoing Hemodialysis: A Short Communication. 2023

Fumiaki Tanaka, and Kei Irie, and Nobuyuki Fukui, and Ryo Horii, and Hirotoshi Imamura, and Masaki Hirabatake, and Hiroaki Ikesue, and Nobuyuki Muroi, and Shoji Fukushima, and Nobuyuki Sakai, and Tohru Hashida
Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan.

BACKGROUND Temozolomide (TMZ) is an alkylating agent used to treat glioblastoma. However, the pharmacokinetics of TMZ to establish a treatment strategy for patients undergoing hemodialysis (HD) remain unclear. In this case report, we evaluated the pharmacokinetics and HD removal rate of TMZ in a patient with glioblastoma undergoing HD to determine optimal dosing of TMZ. METHODS A 78-year-old man with glioblastoma who underwent HD 3 times a week was treated with TMZ concomitant with radiotherapy. One dose of TMZ was prescribed at 75 mg/m 2 on the day before HD and another dose of 37.5 mg/m 2 on the day before non-HD. Peak and trough concentrations (1 hour and 12 hours after dosing, respectively) were evaluated before HD and on non-HD days. HD removal rate of TMZ was calculated based on the predialyzer and postdialyzer plasma concentrations. Furthermore, the TMZ plasma concentrations were measured using liquid chromatography-tandem mass spectrometry. RESULTS The mean plasma peak and trough concentrations ± SD after 75 mg/m 2 TMZ were 2917 ± 914 and 108 ± 17.6 ng/mL, respectively. Those after 37.5 mg/m 2 TMZ dosage were 1305 ± 650 and 53.8 ± 11.8 ng/mL, respectively. The mean HD TMZ removal rate was 84.9 ± 1.9%. CONCLUSIONS TMZ was tolerable in patients undergoing HD. Based on the data from a single individual pharmacokinetic perspective, the pharmacokinetics of TMZ in this patient undergoing HD were comparable with those observed in patients with normal renal function. In addition, it may be reasonable to administer TMZ after HD because of the high HD removal rate.

UI MeSH Term Description Entries
D008297 Male Males
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D003606 Dacarbazine An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564) DTIC,5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide,Biocarbazine,DIC,DTIC-Dome,Decarbazine,Deticene,Dimethyl Imidazole Carboxamide,Dimethyl Triazeno Imidazole Carboxamide,ICDT,NSC-45388,Carboxamide, Dimethyl Imidazole,DTIC Dome,DTICDome,Imidazole Carboxamide, Dimethyl,NSC 45388,NSC45388
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077204 Temozolomide A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA. 8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one,CCRG 81045,CCRG-81045,M&B 39831,M&B-39831,Methazolastone,NSC 362856,NSC-362856,TMZ-Bioshuttle,TMZA-HE,Temodal,Temodar,Temozolomide Hexyl Ester,CCRG81045,M&B39831,NSC362856,TMZ Bioshuttle
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D018906 Antineoplastic Agents, Alkylating A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) Alkylating Agents, Antineoplastic,Alkylating Antineoplastic Agents,Alkylating Antineoplastic Drugs,Alkylating Antineoplastics,Alkylating Drugs, Antineoplastic,Antineoplastic Alkylating Agents,Antineoplastic Drugs, Alkylating,Antineoplastics, Alkylating,Antineoplastic Alkylating Drugs,Drugs, Antineoplastic Alkylating

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