Carl A. Schlagel

Preliminary animal toxicology and human tolerance of anti-herpes agent U-3243

This drug, 4′-[2-nitro-1-(p-tolythio)ethyl] acetanilide, has shown efficacy against herpes simplex infection in animal studies, In tolerance studies in animals, the LD50 was 234 mg/kg intraperitoneally in mice and >8000 mg/kg orally in rats. Given for 20–30 days, the drug was generally well tolerated by rats, dogs, and rabbits. In double-blind, placebo-controlled oral tolerance tests in healthy prison inmates, doses as high as 2 mg/kg—much higher than would be used topically in treating herpes simplex—appeared to be safe. Topical applications under double-blind conditions were well tolerated and caused no important side effects. No serious side effects were found in human tolerance testing with U-3243.

Antibiotic tolerance and serum levels after intravenous administration of multiple large doses of lincomycin

High doses of lincomycin ranging from 4,800 mg. to 8,400 mg. daily for 7 days were infused into 32 healthy volunteers on a 4 times a day basis in saline infusion volumes of 250 ml. given over a 120 minute period. Placebo groups given saline only in a similar manner were used as controls. No gross abnormalities in vital signs occurred at any time, and no statistically significant differences occurred between the drug and placebo groups. The laboratory tests were always within normal limits; there were no shifts or drug‐related findings. All electrocardiograms and audiometric tracings were normal, and there were no changes from prestudy readings. Side effects were minor and few. Serum levels averaged from approximately 24 to 37 flg per milliliter (peaks) and 10 to 12 μg per milliliter (nadir) for the low‐to high‐dose drug groups. The equilibrium state was reached early in the schedule with little or no drug accumulation after 26 doses. The elimination rate constant K averaged 0.0987 how‐1 with a corresponding average half‐life (T1/2) of 7.16 hours.