Factors in the lethality of i.v. phencyclidine in conscious dogs.

1. Pretreatment were pancuronium prevented convulsions and hyperthermia, but had no effect on acidemia or changes in cardiovascular parameters after intravenous (i.v.) infusion of phencyclidine (PCP). 2. While dogs survived higher amounts of PCP, they failed to regain spontaneous respiratory function. 3. Mechanical ventilation alone increased the mean lethal dose/time of PCP and reduced the effects of PCP on arterial systolic pressure, cardiac output, and PCO2. 4. EKG showed ventricular arrhythmias, which progressed to death. 5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm. 6. Blocking of convulsions prevented hyperthermia and acidemia; respiratory support reduced circulatory effects, but respired dogs then died, at higher doses, from a primary myocardial toxicity of PCP.

Nonclinical study requirements for ophthalmic drugs and devices in the United States.

The eye is a unique organ embryologically, immunologically, physiologically and consequently exhibits unique toxicological responses. Toxic responses in the eye may result from topical ocular administration of drugs, intraocular administration or implantation of drugs or devices or may be the result of target organ toxicity following systemic administration of a drug. The primary responsibility of the toxicologist is to establish the safety/toxicity profile for a drug or device under development and thus provide an appropriate risk analysis of the drug/device for human use. For the ophthalmic toxicologist this safety profile must include the appropriate toxicological evaluations to place in perspective the intended use of the drug or device, its effect on the relevant ocular tissues, its potential for adverse systemic effects, if warranted, and the potential risk to the patient in the clincal setting.