The disposition of loxistatin and metabolites in normal and dystrophic hamsters

Abstract

1. The absorption, distribution and excretion of loxistatin were studied in normal and dystrophic hamsters.

2. After oral administration of ¹⁴C-loxistatin to normal hamsters, the plasma level of radioactivity reached a maximum at 0.5 h and declined with an elimination half-life of 2.3 h. The ratios of metabolites M-1 and M-4, which are pharmacologically active, to the total radioactivity in the plasma were 63% and 25% at 0-5 h after dosing, respectively.

3. After oral administration to hamsters, excretion of radioactivity in urine, faeces and expired air during 120 h were 64%, 28% and 6% of the dose, respectively.

4. The highest radioactivity was observed in kidney followed by liver. From the microautoradiographic study, radioactivity was found to be located in the cardiac and skeletal muscle fibre cells, which are target organs of the drug, in both dystrophic and normal hamsters.