METABOLIC-FATE OF PHENOBARBITAL - QUANTITATIVE STUDY OF P-HYDROXY-PHENOBARBITAL ELIMINATION IN MAN

  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (1) , 63-70
Abstract
Biotransformation of phenobarbital (PB) to p-hydroxyphenobarbital (PHPB) was studied quantitatively by GLC in 8 epileptic patients who were receiving an established regimen of antiepileptic drugs including PB. PB and both conjugated and unconjugated PHPB were present in each patients urine; m-hydroxyphenobarbital (MHPB) was not detected despite an assay sensitivity of 0.25 .mu.g/ml. Incubation of the urine with .beta.-glucuronidase, but not with arylsulfatase, liberated PHPB which was, therefore, presumed to be conjugated with glucuronic acid. In general, the patients urine contained more PB than total PHPB. Recovery of the patients total daily dose of PB ranged from 24-77% (mean, 42%). After receiving a single i.v. dose of PB, PB and both conjugated and unconjugated PHPB were found in a normal volunteers urine throughout a 16 day collection period; 30% of the dose was recovered. PB excretion was proportional to urine volume in the volunteer and in 2 additional patients who were made to vary their daily fluid intake. PHPB was not detected in the CSF of 10 patients receiving PB. Neither PB, PHPB nor MHPB were detected in the feces of 4 patients. Metabolites other than PHPB or MHPB may be important in the elimination of PB in man.