Comparative pharmacokinetics and pharmacodynamics of eterobarbital and phenobarbital in normal volunteers.
The comparative pharmacokinetics and pharmacodynamics of single oral doses of eterobarbital (N,N'-dimethoxymethylphenobarbital, DMMP, 400 mg) and phenobarbital (200 mg) were evaluated in a double-blind study in 8 normal volunteers. Following administration of DMMP, no unchanged drug could be detected in serum. The active monomethoxymethyl metabolite (MMP) appeared rapidly in the circulation but its concentration remained generally low and declined below the limit of detection (0.5 micrograms/ml) usually before 9.5 h. Serum levels of DMMP-derived PB increased slowly and reached a peak between 24 and 48 h in most cases. One subject showed an atypical pharmacokinetic profile, characterized by relatively high levels of MMP and a delayed appearance of low levels of PB. After administration of PB, serum drug levels peaked within 1.5 h and remained, at all sampling times, higher than those observed after intake of DMMP. Compared with DMMP, PB induced greater sedative effects as assessed by visual analogue rating scale, critical flicker fusion frequency and multiple sleep latency tests.
Department of Medical Pharmacology, University of Pavia, Italy.
N
N
Barzaghi
G
G
Gatti
R
R
Manni
C A
CA
Galimberti
C
C
Zucca
E
E
Perucca
A
A
Tartara
D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010634:Phenobarbital / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D004338:Drug Combinations; C010451:eterobarb; D010634:Phenobarbital