Experimental cerebral and plasma pharmacokinetic studies of TCNU: implications for brain tumour chemotherapy.
This study of the pharmacokinetics of TCNU, a new nitrosourea, in the rodent has shown that TCNU concentrations in the plasma (ng/ml) and brain (ng/g) are equivalent from 15 min to 4 hours after drug administration. The absolute levels of TCNU obtained with a dose of 100 mg TCNU/kg bodyweight were at most time points, three to four times those obtained with dosage of 25 mg TCNU/kg. The profile of rodent plasma TCNU levels following drug administration is similar to that recorded in humans, with peak TCNU concentrations occurring around 45 min. Since TCNU crosses an intact blood brain barrier (BBB), and clinical Phase I trials have shown it to possess potent antitumour properties. It may be a useful agent in the management of primary and secondary cerebral neoplasia.
Whittle
I R
IR
University Department of Clinical Neurosciences, Western General Hospital, Edinburgh, Scotland.
Macpherson
J S
JS
Smyth
J
J
Miller
J D
JD
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009607:Nitrosourea Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea