Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration.
The distribution of paclitaxel (Taxol) within the central and peripheral nervous system after repeated administration of this antineoplastic agent is still largely unknown. In this study we determined for the first time paclitaxel tissue concentration in the brain, spinal cord, dorsal root ganglia (DRG) and sciatic nerve using an experimental paradigm in the rat which reproduces the features of paclitaxel peripheral neurotoxicity in humans. Pathological confirmation of the onset of paclitaxel-induced peripheral neurotoxicity was performed. In order to achieve reliable results even with low concentrations of paclitaxel, a newly reported analytical method (high-performance liquid chromatography with tandem mass spectrometry) was used. We demonstrated that paclitaxel has easy access to the DRG, where it accumulates, while the lowest concentrations of the drug were measured in the brain. The intermediate concentrations of paclitaxel observed in the sciatic nerve and spinal cord may be due to paclitaxel transport along the centrifugal and centripetal branches of the DRG neuron axons.
Cavaletti
G
G
Department of Neurology, University of Milan Bicocca, S.Gerardo Hospital, Monza (MI), Italy. guido.cavaletti@unimi.it
Cavalletti
E
E
Oggioni
N
N
Sottani
C
C
Minoia
C
C
D'Incalci
M
M
Zucchetti
M
M
Marmiroli
P
P
Tredici
G
G
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel