Larry H Danziger — Page 2

PubMed2002

Intracellular activity of ABT-773 and other antimicrobial agents against Legionella pneumophila.

The intracellular activity of ABT-773 against Legionella pneumophila was compared with azithromycin and ciprofloxacin using HL-60 cells. Against L. pneumophila ATCC 33152 and three clinical isolates the MICs (mg/L) were ABT-773 0.015, ciprofloxacin 0.03 and azithromycin 0.03. At 48 h, the mean percentage inhibition was as follows: 28.5 +/- 5.9% and 32.6 +/- 4.6% at 8 x and 16 x MIC of ABT-773; 38.1 +/- 8.6% and 48.2 +/- 7.0% at 8 x and 16 x MIC of ciprofloxacin; and 26.3 +/- 9.9% and 28.5 +/- 9.9% at 8 x and 16 x MIC of azithromycin. In this study, all three agents were highly active, with ABT-773 demonstrating similar activity to azithromycin against L. pneumophila.

Anti-Bacterial Agents↗

PubMed2002

Lack of effect of nizatidine-induced elevation of gastric pH on the oral bioavailability of dapsone in healthy volunteers.

STUDY 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. DESIGN: Prospective, randomized, crossover, open-label, single-dose pharmacokinetic study. SETTING: Teaching hospital. PATIENTS: Sixteen men were enrolled in the study; data from 11 subjects were evaluable. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION: 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.

Administration, Oral↗