III. Pentobarbital sodium in prolonged‐action form compared with conventional capsules: Serum levels of drug and clinical effects following acute doses

Abstract

Twelve subjects were given acute 200 mg. doses of pentobarbital sodium in four trials at weekly inteTIJals. Two doses were administered as conventional capsules; two as proprietary prolonged‐action preparations (Gradumet). The order of administration was randomized. Mean serum levels of pentobarbital sodium were cOnsistently higher following the capsules, although only significantly greater than from the prolonged‐action medication at 2 hours. First trials of the capsules showed significantly higher levels of the drug than second trials at 4, 8, and 24 hours. No significant differences were found between successive trials of prolonged action medications; however, the range of serum levels was COnsiderable, with much variation within as well as between subjects. Global estimates of the effects indicated that for most subjects the capsule dose had greater intensity and duration. Capsules also appeared to have appreciably more effect as determined by the Clyde mood scale at 2 and 4 hours, but less at 8 hours. No advantage could be found for the prolonged‐action form, which appeared slightly less efficient than the capsules. Biologic variability between trials using the same subject may supersede any advantages of specific pharmaceutical preparations of drug.