Pharmacokinetics of intra-arterially administered pirarubicin in plasma and cerebrospinal fluid of patients with glioma.
The present paper investigates the pharmacokinetics of pirarubicin (THP) in the plasma and cerebrospinal fluid (CSF) of two patients with glioma during hyperosmotic disruption of the blood-brain barrier (HODBBB) and intra-arterial combination chemotherapy. A 42-year-old Japanese man (patient A) with glioblastoma and a 21-year-old Japanese woman (patient B) with astrocytoma received a course of HODBBB and intra-arterial combination chemotherapy with THP, methotrexate, peplomycin, and vindesine. Patient A was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery. Patient B was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery and, immediately thereafter, into the right vertebral artery. Samples of blood and of CSF in the brain ventricle were obtained. THP concentration was measured by HPLC, and the pharmacokinetic parameters of this drug were estimated in plasma and CSF. In both patients, the plasma concentration of THP peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. THP was detectable in CSF beginning 1.0 h after the initiation of infusion, then was slowly eliminated from the ventricle. The maximum CSF concentration of THP was 0.97% of plasma in patient A and 0.89% in patient B. The CSF AUC of THP was 28.4% of plasma in patient A and 13.1% in patient B.
Morikawa
N
N
Department of Hospital Pharmacy, Oita Medical University, Japan.
Mori
T
T
Takeyama
M
M
Hori
S
S
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007261:Infusions, Intra-Arterial; D008727:Methotrexate / Q000008:administration & dosage; D017663:Peplomycin / Q000008:administration & dosage; D014751:Vindesine / Q000008:administration & dosage
D017663:Peplomycin; D004317:Doxorubicin; C027260:pirarubicin; D014751:Vindesine; D008727:Methotrexate