[Pharmacokinetics of MX2, a new morpholino anthracycline, in CSF following intravenous injection].
MX2 x HCl is a new morpholino anthracycline derivative with molecular weight 622.07, and highly lipophilic. In the animal experiments, MX2 was found to cross the blood brain barrier after i.v. injection. Its distribution into the brain was increased by intracarotid injection. In the present study, we examined the distribution of MX2 into the cerebrospinal fluid (CSF) after i.v. administration (5 mg/kg) in normal rabbits. Five min after injection, plasma concentration of MX2 reached to the maximum level (4344.5 ng/ml). CSF concentration of MX2 was at the highest level (75.8 ng/ml) 10 min after injection, and thereafter decreased gradually in parallel with plasma concentration. At 5 hrs after injection, CSF concentration became 26.7 ng/ml, AUC half time of elimination, and mean residence time were 3093.8 ng.hr/ml, 4.57 hrs and 5.10 hrs in plasma and 212.3 ng.h/ml, 5.23 hrs and 7.14 hrs in CSF, respectively. These results indicate that MX2 is able to distribute into CSF after i.v. injection, and expected to be a new anticancer drug for brain and leptomeningeal tumors.
Yamamoto
H
H
Dept. of Neurosurgery, Osaka University Medical School.
Arita
N
N
Ohnishi
T
T
Hiraga
S
S
Izumoto
S
S
Taki
T
T
Higuchi
M
M
Hayakawa
T
T
Shinkai
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002360:Carubicin / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D011817:Rabbits
D000903:Antibiotics, Antineoplastic; C053537:morpholinoanthracycline MX2; D002360:Carubicin