Assessment of doxylamine influence on mixed function oxidase activity upon multiple dose oral administration to normal volunteers.
The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5 mg of doxylamine succinate, placebo, or 30 mg of phenobarbital administered orally every 6 h for 17 days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 micrograms) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.
Thompson
G A
GA
Procter & Gamble Pharmaceuticals, Cincinnati, OH 45242, USA.
St Peter
J V
JV
Heise
M A
MA
Horowitz
Z D
ZD
Salyers
G C
GC
Charles
T T
TT
Brezovic
C
C
Russell
D A
DA
Skare
J A
JA
Powell
J H
JH
D000284:Administration, Oral; D000328:Adult; D004319:Doxylamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000187:drug effects* / Q000378:metabolism; D010919:Placebos; D012016:Reference Values
D010919:Placebos; D004319:Doxylamine; D006899:Mixed Function Oxygenases