Lack of effect of nizatidine-induced elevation of gastric pH on the oral bioavailability of dapsone in healthy volunteers.
OBJECTIVE
To investigate the effect of histamine2 (H2)-receptor antagonist-induced elevation of gastric pH on oral bioavailability of a single dose of dapsone 100 mg.


METHODS
Prospective, randomized, crossover, open-label, single-dose pharmacokinetic study.


METHODS
Teaching hospital.


METHODS
Sixteen men were enrolled in the study; data from 11 subjects were evaluable.


METHODS
Participants received two treatments separated by at least 14 days. Treatment A consisted of a single dose of dapsone 100 mg. Treatment B consisted of a single dose of dapsone 100 mg plus two doses of oral nizatidine 300 mg administered 3-4 hours apart to maintain gastric pH above 6.0. Plasma samples collected before and up to 120 hours after dapsone administration were analyzed for dapsone and monoacetyldapsone (MADDS) by high-performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis.


RESULTS
Gastric pH in the first 6 hours after dapsone administration was above 6.0 for a mean +/- SD of 1.1% +/- 2.9% of the time in the absence of nizatidine and 69.5% +/- 18.0% of the time during nizatidine therapy. The geometric mean dapsone maximum plasma concentration (Cmax) declined by 13% (p<0.01), and median time to Cmax occurred 2 hours later (p<0.01) with nizatidine coadministration compared with dapsone alone. Inclusion of the 90% confidence interval for the mean Cmax ratio within the equivalence interval of 0.8-1.25 demonstrated the lack of clinical significance for this modest decrease in Cmax. Neither the area under the dapsone plasma concentration-time curve from zero to infinity nor the elimination half-life of dapsone were significantly altered by nizatidine. No clinically significant changes were observed in the pharmacokinetics of MADDS with regard to coadministration of nizatidine.


CONCLUSIONS
Elevation of gastric pH by H2-receptor antagonists, such as nizatidine, does not result in clinically important changes in the rate or extent of oral dapsone absorption.
Itokazu
Gail S
GS
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, USA. gitokazu@uic.edu
Fischer
James H
JH
Manitpisitkul
Prasarn
P
Hariharan
Radhika
R
Danziger
Larry H
LH
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003622:Dapsone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D016014:Linear Models; D008297:Male; D016567:Nizatidine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011446:Prospective Studies; D018709:Statistics, Nonparametric
D003622:Dapsone; D016567:Nizatidine