Differences in the pharmacokinetics of cocaine in naive and cocaine-experienced rats.
Enhanced cocaine concentrations in brain and blood observed after an intraperitoneal challenge dose in rats exposed to cocaine for 10 days by subcutaneous administration are traced to a change in the absorption process from the site of an intraperitoneal injection to general circulation. This conclusion is reached by three sets of corroborating results: (a) Adipose tissue of rats treated for 10 days with repeat subcutaneous injections of cocaine did not reveal a buildup of cocaine in sufficient concentrations to account for the twofold increase in brain and blood concentrations seen during intraperitoneal administration; (b) administration of the drug by an intravenous route after 10-day cocaine treatment did not show a significant difference between treatment and control groups; (c) nonlinear regression on the intravenous and intraperitoneal data sets using a two-compartment open model indicated a difference in the absorption process but not in the metabolic and blood-brain transfer processes.
Pan
H T
HT
Department of Chemistry, Emory University, Atlanta, Georgia 30322.
Menacherry
S
S
Justice
J B
JB
D000042:Absorption; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003042:Cocaine / Q000493:pharmacokinetics*; D004361:Drug Tolerance; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013997:Time Factors
D003042:Cocaine