Diurnal variation in the pharmacokinetics of nizatidine in healthy volunteers and in patients with peptic ulcer disease.
Six healthy volunteers and six patients with asymptomatic duodenal ulcer disease received placebo or 300 mg nizatidine once at night or twice daily (morning and evening) for a week in a random, cross-over fashion. Steady-state serum nizatidine concentrations and gastric pH were measured over a 24-hour period. No significant differences in the pharmacokinetic indices were observed between the healthy volunteers and patients with duodenal ulcer disease. In patients with duodenal ulcers, significantly lower peak serum concentrations, longer half-life (t1/2) and larger volume of distribution (Vd) were observed after the night doses compared with the daytime doses. The diurnal variation in drug kinetics between the nighttime and daytime doses in the twice daily regimen may be caused by a slower absorption rate, paralleled with a higher extent of distribution. Despite lower serum nizatidine concentrations, gastric pH was higher in the evening than in the daytime; it is speculated that this was due to a time-dependent enhanced distribution of the H2-receptor blocker into the site of action.
Jamali
F
F
Faculty of Pharmacy, University of Alberta, Edmonton, Canada.
Thomson
A B
AB
Kirdeikis
P
P
Tavernini
M
M
Zuk
L
L
Marriage
B
B
Simpson
I
I
Mahachai
V
V
D000328:Adult; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004381:Duodenal Ulcer / Q000378:metabolism*; D005260:Female; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016567:Nizatidine / Q000493:pharmacokinetics*
D006635:Histamine H2 Antagonists; D016567:Nizatidine