Inhibitory Effects of Several Fluoroquinolones on Feline CYP1A and 3A in Hepatic Microsomes

In this study, the effects of several fluoroquinolones (FQs), such as Ciprofloxacin (CPFX);Orbifloxacin (OBFX);Norfloxacin (NFX);Ofloxacin (OFX);and Enerofloxacin (EFX) on activities of both Cytochrome P450 1A (CYP1A) and Cytochrome P450 3A (CYP3A) of feline microsomes by in vitro tests were studied. Ethoxyresorufin O-deethylation (EROD) and Midazolam 1' hydroxylation and 4-hydroxylation (MDZ1'H and MDZ4H) were analyzed by High Performance Liquid Chromatography (HPLC). All the FQs inhibited the reactions by a competitive or noncompetitive and irreversible manner. The inhibitory constants (Ki) were as followings: CYP1A;ranged from 0.12 to 1.23 mM for NFX, OBFX, EFX, CPFX, OFX and CYP3A, for MDZ1'H;ranged from 5.8 to 35 and MDZ4H;9 to 29 mM, respectively. As these values are higher by 24 to 200-times of given single clinical dose of serum levels after application of FQs. It indicates that if co-administrated with these FQs by reversible inhibitory manner, the inhibition of CYP1A and CYP3A effect on CYP1A and 3A actions is not very significant to cause drug interaction with above mentioned enzyme substrates. Out of the FQs tested, CPFX and NFX for CYP1A, and CPFX for CYP3A showed irreversible inhibitory effects (time-dependent), so it has been concluded that these drugs may cause drug-drug interaction by accumulation, when they are repeatedly administrated. Since EFX is biotransformed to CPFX by the liver, it could have the identical risk too.

Comparative Evaluation of Different Treatment for Purulent Wounds in Dogs

To compare the healing of purulent wounds with Shilajit dressing vs. Vishnevsky dressing in dogs with purulent wounds of >2 weeks of duration, eight dogs were chosen from same ages in two groups i.e., Shilajit and Vishnevsky dressing group. Dressing was done on every day basis for more than two weeks of follow up period. Main outcome of healing measure was completed at three weeks. Wound healing status was assessed at three days intervals till end of three weeks. Shilajit treated achieved complete decrease in the wound surface area, effect of healing score in Shilajit dressing group in comparison to the Vishnevsky dressing group at p > 0.05 level of significance. Shilajit is highly effective in achieving a characteristic feature of regenerative and granulation healing of purulent wounds as compared to Vishnevsky dressing group in dogs.