In-vivo microdialysis study of the distribution of cisplatin into brain tumour tissue after intracarotid infusion in rats with 9L malignant glioma.
Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats. Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg-1) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUC, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.
Nakashima
M
M
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Shibata
S
S
Tokunaga
Y
Y
Fujita
H
H
Anda
T
T
Arizono
K
K
Tomiyama
N
N
Sasaki
H
H
Ichikawa
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry / Q000378:metabolism*; D002343:Carotid Artery, Internal; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005910:Glioma / Q000737:chemistry / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009368:Neoplasm Transplantation; D010984:Platinum / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin