title: Pharmacokinetics and safety of MP-376 (levofloxacin inhalation solution) in cystic fibrosis subjects.
abstract: The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (C(max)) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean C(max) for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin C(max) ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development.
authors: Nemours Children's Clinic, 496 S. Delaney Ave., Suite 406A, Orlando, Florida 32801, USA.
authors: David E
authors: DE
authors: Geller
authors: Patrick A
authors: PA
authors: Flume
authors: David C
authors: DC
authors: Griffith
authors: Elizabeth
authors: E
authors: Morgan
authors: Dan
authors: D
authors: White
authors: Jeffery S
authors: JS
authors: Loutit
authors: Michael N
authors: MN
authors: Dudley
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D012996:Solutions
chemical_list: D000900:Anti-Bacterial Agents; D012996:Solutions; D064704:Levofloxacin; D015242:Ofloxacin