title: Post-exposure therapy of inhalational anthrax in the common marmoset.
abstract: The aim of this study was to compare the pharmacokinetics and efficacy of ciprofloxacin as post-exposure therapy against inhalational anthrax in the common marmoset (Callithrix jacchus) with other non-human primate models in order to determine whether the marmoset is a suitable model to test post-exposure therapies for anthrax. Pharmacokinetic (PK) and efficacy studies with ciprofloxacin were performed in the marmoset. Ciprofloxacin plasma pharmacokinetics were determined in six animals in separate single-dose and multiple-dose studies and were analysed by high-performance liquid chromatography (HPLC). A separate group of marmosets was exposed to ca. 100× the 50% lethal dose (LD(50)) of Bacillus anthracis Ames strain by the airborne route. On Day 5 of a twice-daily dosing regimen of 17.5 mg/kg, the ciprofloxacin half-life (t(1/2)), maximum drug concentration (C(max)) and area under the concentration-time curve (AUC) in marmoset plasma were 1.9 h, 2.1 μg/mL and 7.9 μg/mL/h, respectively. Naïve untreated control animals succumbed to infection by Day 9. All animals treated with ciprofloxacin, started on the day of exposure and continued for 10 days, remained healthy during the treatment period. Two antibiotic-treated animals (33%) died after withdrawal of antibiotic therapy, attributed to the germination of residual spores. In conclusion, in many respects the marmoset appears to respond to B. anthracis in a similar way to the macaque, suggesting that this small non-human primate is an acceptable, practical alternative model for the evaluation of medical countermeasures against respiratory anthrax infection.
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. mnelson@dstl.gov.uk
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Stagg
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stevens
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brown
authors.forename: Peter C
authors.initials: PC
authors.lastname: Pearce
authors.forename: A J H
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Lever
mesh_terms: D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001408:Bacillus anthracis / Q000187:drug effects / Q000472:pathogenicity; D002144:Callithrix; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013171:Spores, Bacterial / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin