Pharmacokinetics of a benzodithiin (RD3-0028) following aerosol treatment in rat.
1. RD3-0028, a benzodithiin compound, has potent antiviral activity against respiratory syncytial virus (RSV) in cell culture. The compound also inhibits growth of RSV and improves pathologic changes of interstitial pneumonia in the immunosuppressed mouse when delivered by small-particle aerosol. 2. In the present study, the absorption, distribution and excretion of 14C-RD3-0028 were compared in rat following either a single aerosol treatment or oral administration. 3. The plasma concentration was maintained at the same level from 5 min to 1 h, and decreased with a half-life of 2.2 +/- 0.1 h for 1-8 h. 4. The excretion of radioactivity in the urine and faeces at 24 h after aerosol treatment was 89.3 and 4.5%, respectively, indicating that almost all the radioactivity was rapidly excreted in the urine. The excretion of total radioactivity was 98.9% within 168 h. 5. The concentrations of radioactivity in the lung and trachea following aerosol treatment were higher than those in other tissues, and were detected even at 72 h. 6. These results suggest that the aerosol treatment might be useful for delivering RD3-0028 to the respiratory tract of RSV-infected patients.
Sudo
K
K
Rational Drug Design Laboratories, Fukushima, Japan. sudou.kenji@yamanouchi.co.jp
Yoshida
K
K
Konno
K
K
Ninomiya
S
S
Hibino
S M
SM
Shigeta
S
S
Yokota
T
T
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy; D014018:Tissue Distribution; D014132:Trachea / Q000378:metabolism
D000336:Aerosols; D000998:Antiviral Agents; D002250:Carbon Radioisotopes; D006571:Heterocyclic Compounds; C119093:RD3 0028