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Titolo:
Liquid dose pulmonary instillation of gentamicin PulmoSpheres (R) formulations: Tissue distribution and pharmacokinetics in rabbits
Autore:
Smith, DJ; Gambone, LM; Tarara, T; Meays, DR; Dellamary, LA; Woods, CM; Weers, J;
Indirizzi:
Alliance Pharmaceut Corp, San Diego, CA 92122 USA Alliance Pharmaceut Corp San Diego CA USA 92122 , San Diego, CA 92122 USA
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 11, volume: 18, anno: 2001,
pagine: 1556 - 1561
SICI:
0724-8741(200111)18:11<1556:LDPIOG>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESPIRATORY-DISTRESS SYNDROME; EXOGENOUS SURFACTANT; GAS-EXCHANGE; VENTILATION; PERFLUOROCARBON; INTRATRACHEAL; PERFLUBRON; PARTICLES; LUNGS;
Keywords:
gentamicin; PulmoSpheres (R); perflubron; lung; drug delivery; LiquiVent (R);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Smith, DJ Alliance Pharmaceut Corp, 3040 Sci Pk Rd, San Diego, CA 92122 USA Alliance Pharmaceut Corp 3040 Sci Pk Rd San Diego CA USA 92122 A
Citazione:
D.J. Smith et al., "Liquid dose pulmonary instillation of gentamicin PulmoSpheres (R) formulations: Tissue distribution and pharmacokinetics in rabbits", PHARM RES, 18(11), 2001, pp. 1556-1561

Abstract

Purpose. To assess the pharmacokinetics and biodistribution of gentamicin,delivered as PulmoSpheres((R)) formulations in rabbit serum and lung tissue following intratracheal instillation in a perflubron vehicle. Methods. Rabbits were anesthetized, intubated, and mechanically ventilatedwith O-2 (FiO(2) = 0.50). Animals were then given 5 mg/kg gentamicin either intravenously, intramuscularly (IM), or intratracheally (IT) gentamicin PulmoSpheres((R)) formulation, instilled in 1.8 ml/kg of liquid perflubron vehicle. Serum and lung lobe sections were collected at multiple time pointsand assayed for gentamicin content. Results. Serum gentamicin levels peaked at 64.7 mug/ml, 11.2 mug/ml, and 5.0 mug/ml following intravenous, IM, and IT administration, respectively. Absolute bioavailability at 8 h for IM administration was 76.8% and 57.0% when delivered IT. Although peak lung levels of drug were reached within I h,total lung gentamicin concentration after IT administration was more than two orders of magnitude greater than that achieved following IM administration (680,540 vs. 4,985 mug min, respectively) with significant levels of the antibiotic remaining in the lung even after 1 week. Conclusions. High levels of gentamicin in lung tissue can be achieved by instillation of a gentamicin PulmoSpheres((R)) formulation in a perflubron vehicle, termed liquid dose installation, without reaching toxic systemic levels allowing for increased local delivery of agents such as gentamicin at the site of the infection.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 17:51:44