Effects of ethanol and delta 9-tetrahydrocannabinol on phencyclidine disposition in dogs.

A three-way crossover study was performed to determine the influence of delta 9-tetrahydrocannabinol (THC) and ethanol (EtOH) separately upon phencyclidine (PCP) disposition in dogs. Seven dogs were given three single dose treatments: 1.5 mg PCP kg-1 i.v., 1.5 mg PCP kg-1 i.v. with 0.4 mg kg-1 THC i.v., and 1.5 mg PCP kg-1 i.v. with 1.25 g EtOH kg-1 i.v. PCP was measured in plasma samples collected for 24 h after administration of each treatment, with several pharmacokinetic parameters calculated from the plasma concentration vs time data. The PCP serum Cls values were significant change in V beta or t1/2. EtOH did not induce significant changes in any PCP pharmacokinetic parameter, although mean Cls and V beta were increased. These results confirm the observed THC inhibition of PCP metabolism, and suggest that the enhanced pharmacologic action of PCP by THC may result from higher serum PCP concentrations. These results further suggest that enhanced PCP actions by acute EtOH administration may result from increased PCP distribution to the CNS.

Estimation of theophylline clearance during continuous arteriovenous hemofiltration.

Pharmacologic agents and other non-protein-bound compounds smaller than 5,000 daltons have the potential to be removed by continuous arteriovenous hemofiltration (CAVH). A proposed method for estimating drug clearance by CAVH (ClCAVH) equates ultrafiltrate clearance to the product of the sieving coefficient and the average ultrafiltration rate. This simplified approach for estimating ClCAVH would be a clinically useful method for calculating replacement doses, as it economizes on the sampling and analytical requirements associated with the conventional method. Presented are some theoretical considerations and a brief evaluation of the accuracy of this proposed method. The evaluation was conducted using an animal model whereby CAVH was performed in four male beagles. During the hemofiltration period, an i.v. bolus of theophylline, 6 mg/kg, was administered over 15 s. Samples for analysis of theophylline were collected from the arterial, venous, and ultrafiltrate ports at 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, 360, and 480 min following dosage administration. The volume of ultrafiltrate produced during each collection interval was measured. Theophylline serum concentrations were determined by a high performance liquid chromatography assay. Statistically, the simplified method was found to result in significantly (p less than 0.05) larger estimates of ultrafiltrate clearance when compared to the conventional method. However, the average magnitude of difference was only 9% and does not constitute a clinically significant margin between the two methods.

Ethanol and aging effects on movement initiation can be dissociated from general behavioral impairment using a high-speed lever-release task in rats.

An animal model of human reaction time was used to assess the effects of ethanol on reactive capacity (RC) as a function of age. Three doses of ethanol (0.5, 1.0 & 1.5 g/kg of 20% v/v, i.p.) were confirmed by gas chromatographic analysis of blood samples taken immediately following every behavioral test. Fisher 344 rats were trained to use their forepaws to hold down a lever until the onset of a buzzer and light that signalled impending foot shock, which occurred within 200-1000 msec of the stimulus. All rats were shaped to release the lever faster than 200 msec, which permitted them to avoid all shock under saline treatment. In the first experiment, only young adult rats (3-4 mos) were tested. Ethanol caused a dose-dependent impairment of RC. In a second experiment, rats aged 4, 12 and 24 mos were tested. As in previous work, RC was reduced by age. Ethanol caused a dose-dependent impairment of response speed (as indicated by the average of the fastest five RTs) that was exaggerated in the 24 mo-old rats. Ethanol also appeared to amplify the trial-by-trial variability in RC that was typical of the old rats under saline conditions. Nevertheless, if given enough time (1000 msec) most rats (except for a few in the oldest group) were able to avoid shock under ethanol as reliably as under saline conditions, even at the highest dose. Thus, ethanol specifically slowed reaction time while sparing memory and motivational and motor capacities required for success in this task. Both extensive practice and pre-test warm up sessions modified the effects of ethanol; however they did not do so differentially across ages.

Seroprimatology of chimpanzees: blood-group distribution as a "racial" characteristic.

Significant differences in the distribution of human-type and simian-type blood groups have been demonstrated in chimpanzees classified into subspecies or "races" on the basis of morphological traits. The differences in chimpanzees are analogous to racial differences in the distribution of blood groups in man.