This thesis reports the pharmacokinetics of zidovudine (AZT) and stavudine (d4T) in the cerebrospinal fluid (CSF) in a novel rabbit model following
intrathecal administration. The involvement of
active transporters in the disposition of these two drugs was also investigated. In this research, thirty-two New Zealand White rabbits were used and surgically prepared prior to drug administration In the infusion studies, AZT or d4T was given either as an 8-hr intrathecal infusion alone (5 μg/min) or co-infusion (2.5 μg/min) with an organic anion
transporter inhibitor, probenecid (PBD) (0.5 μg/min). In the bolus studies, AZT or d4T was given as a single intrathecal dose (500 μg). Free…
