An Animal Model for Simultaneous Pharmacokinetic/Pharmacodynamic Investigations: Application to Cocaine

Evaluation of the Blood-Brain Barrier Transport, Population Pharmacokinetics, and Brain Distribution of Benztropine Analogs and Cocaine Using in Vitro and in Vivo Techniques

“…Dose-normalized AUC brain was significantly higher for the BZT analogs compared with cocaine. In addition, AUC brain / AUC plasma ratio for cocaine was ϳ2.0, a value in accordance with previously reported values (Pan and Hedaya, 1998;Javaid and Davis 1993). AHN 2-003, was found to have the smallest AUC ratio of 2.1 in comparison with 2.0 for cocaine, although this compound had the highest Vd ss .…”

Evaluation of a pharmacokinetic hypothesis for reduced locomotor stimulation from methamphetamine and cocaine in adolescent versus adult male C57BL/6J mice

“…While dose, strain, and type of administration all affect pharmacokinetics, our estimates of cocaine and methamphetamine concentrations in the brain and blood are within the range observed in other studies for methamphetamine (Brien et al 1978;Fornai et al 1999;Hendrickson et al 2004;Won et al 2001) and cocaine (Azar et al 1998;Benuck et al 1987;Miller et al 1996;Pan and Hedaya 1998;Reith et al 1987). Additionally, the primary routes of metabolism in mice (Boyer and Petersen 1992;Shuster et al 1983) are similar to those in rats (Estevez et al 1977) and humans (Bencharit et al 2003;Brzezinski et al 1997).…”

Pharmacodynamic Assessment of the Benztropine Analogues AHN-1055 and AHN-2005 Using Intracerebral Microdialysis to Evaluate Brain Dopamine Levels and Pharmacokinetic/Pharmacodynamic Modeling

“…Studies have shown DA levels to increase within 5-10 min after i.v. administration of cocaine (17,18). Microdialysis experiments observed a 300% increase in DA levels over baseline within 10 min after intramuscular dosing of cocaine to squirrel monkeys (19).…”