Pharmacokinetics of physostigmine intramuscularly administered to guinea pigs.

Physostigmine pharmacokinetics was determined in guinea pigs following im administration of 5-146 micrograms/kg. Eighteen male guinea pigs were divided into three equal groups and given dosages of 5, 27, and 146 micrograms/kg, respectively. Physostigmine was given in the right hind limb and blood samples were collected at various times up to 300 min postinjection via an indwelling carotid catheter. Unbound physostigmine plasma concentrations were analyzed by HPLC. The concentration-time profile for each animal was fitted to standard pharmacokinetic models. A one-compartment open model with first-order absorption and elimination provided the best fit. For all dosage groups, physostigmine concentrations peaked in approximately 30 min. Apparent volumes of distribution (assuming 100% bioavailability) ranged from 1.9 to 2.2 L/kg. Systemic clearances and elimination half-lives were 30-36 mL/min/kg and 40-50 min, respectively. The area under the concentration-time curve and the Cmax were linearly related to the dose, indicating pharmacokinetic linearity. In conclusion, physostigmine, intramuscularly administered to the guinea pig, is absorbed, distributed, and eliminated rapidly, and the pharmacokinetics behave linearly within the 5-146-micrograms/kg dosage range.

Effects of physostigmine on the cardiopulmonary system of conscious pigs.

Physostigmine, as a pretreatment candidate for nerve agent poisoning, was examined for cardiopulmonary side effects. Cardiovascular and pulmonary parameters were monitored in unanesthetized domestic pigs which received pulmonary arterial infusion of 5 micrograms/kg/min physostigmine salicylate for 2 hr. A level of 74% inhibition of red blood cell (RBC) acetylcholinesterase (AChE) activity was attained in 45 min, and this level of carbamylation increased only slightly during the remaining infusion period. In addition to this large change in AChE activity, minor changes were observed in hematocrit, heart rate, body temperature, mean aortic pressure, pulmonary arterial wedge pressure, and pulmonary artery pressure. Typically, these parameters showed a trend toward elevated levels. Blood gases, pH, respiratory rate, tidal and minute volume, cardiac output, nonelastic resistance, and dynamic compliance were not significantly different from baseline values. The unanesthetized pig responds to physostigmine in a manner similar to that reported for other species and appears to be a suitable model for evaluating cardiopulmonary effects of cholinesterase inhibitors.

Vitamin E and periodontitis in the rat.

This investigation was designed to study the effect of vitamin E on the course of periodontitis in thirty-six adult male albino rats. The rats were divided into three groups of twelve and placed on test diets which consisted of pelleted feed that either was deficient in, or contained adequate and high amounts of, vitamin E. After the animals had been on their respective diets for 8 weeks, a local irritant in the form of a stainless steel wire was placed around the maxillary left second molar of each animal. The wire served both as a mechanical irritant and as a collector of plaque and debris. Six weeks after the wire was placed, the animals were killed and the periodontium was examined histologically. Migration of the epithelial attachment, alveolar bone level, and numbers of inflammatory round cells were then evaluated on both sides of the maxilla. Multivariate analysis of variance was used to determine significant difference in the parameters. The results of this experiment indicate that a deficiency of vitamin E does not cause increased destruction of the periodontium in the presence of periodontitis. Moreover, no beneficial effects from the therapeutic use of vitamin E to combat periodontitis were found.