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An animal model suitable for pharmacokinetic/pharmacodynamic investigations is described. This model allows drug administration via different routes, serial blood sampling, serial brain ECF sampling, and monitoring the cardiovascular functions without touching the animal. This rat model was utilized to study the relationship between cocaine pharmacokinetics(More)
We investigated the effect of intravenous alcohol coadministration on the pharmacokinetics of cocaine in awake, freely moving rats using the microdialysis technique. Alcohol coadministration resulted in faster rate of cocaine absorption after intraperitoneal administration leading to higher cocaine plasma concentration. The higher plasma cocaine(More)
Sildenafil is the first oral therapeutic agent for the management of male erectile dysfunction. Its oral bioavailability is only 40% due to extensive presystemic elimination, mainly by CYP3A4. This study examined the effect of coadministration of ciprofloxacin or clarithromycin, which inhibit CYP3A4, on the bioavailability and pharmacokinetics of(More)
The kinetics of zidovudine (AZT) distribution into rabbit cerebrospinal fluid (CSF) were studied during continuous infusion of AZT and after iv bolus administration. The CSF/plasma steady-state AZT concentration ratio was 0.192 +/- 0.003. That this ratio is less than unity, and the clearance from the CSF due to bulk flow is much smaller than the total(More)
The pharmacokinetics of zidovudine in the rabbit were studied during coadministration of probenecid at two infusion rates. Each animal (n = 6) served as its own control during an initial 8-hr infusion of zidovudine. In the second 8-hr infusion period, probenecid was coadministered with zidovudine. Urine samples were collected by bladder flush hourly for 19(More)
The effect of alcohol coadministration on cocaine pharmacokinetics and pharmacodynamics was investigated in awake, freely moving rats. Cocaine plasma and brain extracellular fluid (ECF) concentration-time profiles were characterized after intraperitoneal (ip) administration of 30 mg/kg cocaine to rats that were pretreated with either normal saline or(More)
This experiment was designed to investigate the effect of pretreatment with cocaine and alcohol on cocaine pharmacokinetics and pharmacodynamics. Four groups of rats (n = 8 per group) received one of the following pretreatments for two weeks: none, alcohol (10% v/v in drinking water), cocaine (15 mg/kg/day ip), and alcohol+cocaine (10% v/v in drinking water(More)
The effects of the beta-adrenergic antagonist propranolol on the locomotor stimulating, neurochemical, and reinforcing effects of cocaine were examined in rats. In Experiment 1, propranolol (1, 3 and 10 mg/kg, IP) produced a dose-dependent increase in the motor stimulant effects of cocaine without affecting basal motor activity. Atenolol, a peripherally(More)
The effect of probenecid on the renal excretion of zidovudine (3'-azido-3'-deoxythymidine; AZT) and its distribution into CSF was studied in the rabbit. Although probenecid is chemically unrelated to AZT, it has been shown that probenecid inhibits AZT elimination in Acquired Immunodeficiency Syndrome (AIDS) patients. The effect of probenecid on the renal(More)
A sensitive, specific and precise HPLC-UV assay was developed to quantitate cocaine (COC) and its metabolites benzoylecgonine (BE), norcocaine (NC) and cocaethylene (CE) in rat plasma. After adding 50 microl of the internal standard solution (bupivacaine, 8 microg/ml) and 500 microl of Sørensen's buffer (pH 6) to 100 microl of rat plasma sample, the mixture(More)