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Journal of Pharmacology And Experimental Therapeutics, Vol. 111, Issue 4, 425-435, 1954
Copyright © 1954 by American Society for Pharmacology and Experimental Therapeutics

PHENOBARBITAL: STUDIES OF ELIMINATION, ACCUMULATION, TOLERANCE, AND DOSAGE SCHEDULES

Thomas C. Butler 1, Collins Mahaffee 1, and William J. Waddell 1

1 Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

An ultraviolet spectrophotometric method is described for the determination of phenobarbital in plasma. This method has been applied to several problems pertaining to the clinical use of the drug.

In eleven human subjects the proportion of phenobarbital eliminated from the plasma in the course of one day was found to lie within the limits of 11 and 23 per cent.

Administration of phenobarbital at daily intervals or more frequently leads to accumulation.

Both in man and in the dog the effects associated with a given plasma concentration of phenobarbital diminish over the course of the first few days of administration. Tolerance to the hypnotic effects in man more than keeps pace with accumulation and completely obscures any clinical evidence of accumulation.

In chronic dosage schedules in man, one dose of phenobarbital daily results in only small proportional fluctuations of plasma concentration during the day. It is dubious whether there is any practical advantage in giving the drug in more than one dose daily or in forms in which it is released gradually.

Submitted on March 23, 1954




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Copyright © 1954 by the American Society for Pharmacology and Experimental Therapeutics.