title: Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages.
abstract: The therapeutic efficacies of liposome-encapsulated ofloxacin and clarithromycin against Mycobacterium avium-M. intracellulare (MAI) were evaluated in a model of intramacrophage infection. Liposome encapsulation was found to markedly enhance the uptake of each of the drugs by human macrophages. The human blood-derived macrophages were infected at day 7 of culture with MAI. Treatment was initiated 24 h after the infection, and the number of intracellular bacteria was determined at days 2, 3, and 4. Liposome entrapment of either ofloxacin or clarithromycin significantly (P < 0.005) enhanced the activities of the drugs when compared with the antimycobacterial effects of equivalent concentrations of the free (unentrapped) drugs. The drugs were used at concentrations close to their clinically achievable peak levels. The efficacy of clarithromycin, either in the free or liposome-entrapped form, was markedly higher than that of ofloxacin. Liposome-encapsulated ofloxacin or clarithromycin plus ethambutol was, in each case, more effective in organism eradication (P < 0.005) than each agent used singly. These results suggest that liposome-encapsulated clarithromycin may be more effective than the free form of the drug against MAI infections in vivo, and the use of a combination therapy with ethambutol could further enhance the efficacy.
authors.affiliation: Department of Pharmacy, Hartford Hospital, Connecticut 06115.
authors.forename: C O
authors.initials: CO
authors.lastname: Onyeji
authors.forename: C H
authors.initials: CH
authors.lastname: Nightingale
authors.forename: D P
authors.initials: DP
authors.lastname: Nicolau
authors.forename: R
authors.initials: R
authors.lastname: Quintiliani
mesh_terms: D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004337:Drug Carriers; D004977:Ethambutol / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D004977:Ethambutol; D015242:Ofloxacin; D017291:Clarithromycin