Pharmacokinetics of doxylamine, a component of Bendectin, in the rhesus monkey.
The elimination of doxylamine and metabolites was determined after iv administration of [14C]doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly increased and the polar doxylamine metabolites were significantly decreased as the iv doxylamine succinate dose was increased. The plasma elimination of gas chromatograph (GC)-detected doxylamine was determined after oral administration of Bendectin (doxylamine succinate and pyridoxine hydrochloride) at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose increased, the clearance of doxylamine decreased. A statistically evaluated fit of the oral data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data.
Slikker
W
W
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Holder
C L
CL
Lipe
G W
GW
Bailey
J R
JR
Young
J F
JF
D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004025:Dicyclomine; D004319:Doxylamine / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D007408:Intestinal Absorption; D008253:Macaca mulatta; D008954:Models, Biological; D011736:Pyridoxine / Q000493:pharmacokinetics*
D004338:Drug Combinations; C004454:dicyclomine, doxylamine, pyridoxine drug combination; D004025:Dicyclomine; D004319:Doxylamine; D011736:Pyridoxine