Blood-brain barrier passage of azidothymidine in rats: effect of insulin.
Azidothymidine (AZT) crosses the blood-brain barrier (BBB) of 6-8 week old Sprague-Dawley male white rats (Oldendorf technique, ipsilateral cerebral hemisphere) with a brain-uptake index (BUI) of 5.4 +/- 0.8 (mean +/- S.D., n = 13, range 4.4-6-6) using 14C-antipyrine as the diffusible standard. Pretreatment of the animals with the higher doses of insulin (0.6 or 1.0, but not 0.1, 0.2, or 0.3 units per rat, 3 or 10 min. before decapitation) resulted in higher values for the BUI of AZT in most individual animals. In the group of rats treated with 1.0 unit of insulin 10 min. before decapitation, a statistically significant increase in the BUI was observed. Some possible clinical applications of this pharmacologic strategy are discussed.
Ayre
S G
SG
Department of Family Medicine, University of Health Sciences, Chicago Medical School, IL 60064.
Skaletski
B
B
Mosnaim
A D
AD
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015215:Zidovudine / Q000493:pharmacokinetics*
D007328:Insulin; D015215:Zidovudine