Pharmacokinetics and tissue distribution of the nonadecapeptide Moli1901 in rats and mice.
1. Administration of aerosolized, radiolabelled Moli1901 (duramycin, 2622U90), a 19 amino acid polycyclic peptide, to rats resulted in the deposition of high amounts of radiolabel in the respiratory tract, with deposited radiolabel persisting almost unchanged through 7 days after dosing. Little to no radiolabel was present in the bloodstream of these rats. 2. Rats absorbed little radiolabel after p.o. administration, with nearly all of the dose excreted in the faeces by 2 days after dosing. 3. At 7 days following an intravenous dose, rats excreted 54% of the radiolabel in faeces and 5.4% in the urine, with 44% remaining in the carcass, primarily in the liver (33%). 4. Following an intratracheal instillation dose to rats, radiolabel was eliminated from the pulmonary system with a half-life of 64 days. Excretion was almost exclusively via faeces, with an elimination half-life of 52 days. Plasma and blood concentrations in these animals were uniformly <1 ng eq. ml(-1) at all sampling times. 5. Results in mice given intravenous and oral doses were consistent with those observed in rats. 6. Prolonged retention of Moli1901 in pulmonary tissue supports its use in the treatment of respiratory diseases.
McNulty
M J
MJ
GlaxoSmithKline, Inc., Research Triangle Park, NC 27709, USA.
Hutabarat
R H
RH
Findlay
J W A
JW
Devereux
K
K
Knick
V C
VC
Harvey
R J
RJ
Molina
L
L
D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007442:Intubation, Intratracheal; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013462:Sulfur Radioisotopes; D014018:Tissue Distribution
D000336:Aerosols; D000900:Anti-Bacterial Agents; C477246:Moli1901; D010456:Peptides, Cyclic; D013462:Sulfur Radioisotopes