Metabolism of dimethoxymethyl phenobarbital (eterobarb) in patients with epilepsy.
The metabolism of dimethoxymethyl phenobarbital (DMMP) was investigated in 6 epileptic patients using deuterium-labeled drug measured by integrated gas chromatography/mass spectrometry. Following an oral dose of 120 mg, none of the parent compound appeared in serum, urine, or saliva in spite of a measurement sensitivity of less than 0.05 nmol/ml. A metabolite, monomethoxymethyl phenobarbital (MMP), was detected in all patients, with peak serum concentrations averaging 1.96 nmol/ml at 1.3 hours. Phenobarbital was the major metabolite detected, and it reached peak levels in 6 to 12 hours. Two of the patients were continued on DMMP therapy for several months and then administered a pulse dose of deuterated drug. Again no DMMP was detectable. Steady-state drug administration had no effect on the kinetics of metabolism of either MMP or phenobarbital although peak serum concentrations were lower for both metabolites. In the urine of 5 patients an unidentified labeled fragment was detected that does not appear in urine from patients taking phenobarbital. From these pharmacokinetic studies it appears likely that the anticonvulsant activity of DMMP results from its metabolic conversion to phenobarbital.
D000293:Adolescent; D000328:Adult; D004827:Epilepsy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D012463:Saliva / Q000032:analysis; D014018:Tissue Distribution
C010451:eterobarb; D010634:Phenobarbital