Qualitative and quantitative studies of methylphenobarbital metabolism in man.
The accumulation of methylphenobarbital (MPB) and phenobarbital (PB) in plasma in two volunteers who were given continuous once-daily oral doses of MPB for 3 weeks was demonstrated by use of a selected ion-monitoring GC/MS assay. It was shown that the PB concentration exceeded the MPB concentration in plasma after about day 4, and that both barbiturates achieved plateau concentrations after about 2 weeks. GC/MS studies on the urine of these volunteers permitted the identification of several new metabolites of MPB. These included 5-ethyl-5-(4-hydroxyphenyl)-1-methylbarbituric acid (p-OH-MPB), and the 3-O-methylcatechols of both MPB and PB. The meta-isomers of hydroxy-MPB and hydroxy-PB were identified in urine extracts, but were shown to be methodological artifacts. Quantitative studies, with use of a HPLC assay, were carried out for p-OH-MPB, PB and p-OH-PB in urine, and it was shown that these three substances collectively accounted for some 50% of the administered dose (greater than 30% as p-OH-MPB).
D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D008297:Male; D008618:Mephobarbital / Q000008:administration & dosage / Q000378:metabolism*; D010634:Phenobarbital / Q000378:metabolism*
D008618:Mephobarbital; D010634:Phenobarbital