Abstract

In present times, there has been interest in multi-drug combinations for treatment of ocular infections, which are more commonly antibiotics and analgesics. Ciprofloxacin and diclofenac sodium were used concomitantly and pharmacokinetic drug-drug interactions between them were studied. To investigate disposition kinetics of ciprofloxacin eye drops (0.3%) alone and with co-administration of diclofenac sodium eye drops (0.1%) for pharmacokinetic drug-drug interaction(s). A randomized clinical trial was conducted in 84 human volunteers and the aqueous humor samples were collected from the eyes at various time intervals and concentration of ciprofloxacin in aqueous humor was determined using a validated reversed-phase high performance liquid-chromatography/ultraviolet detection method. The results were subjected to statistical analysis to determine whether a statistically significant difference was observed between the two groups. The mean age of the patients in this study ranged from 40 to 83 years, and gender distribution was 46.0% female and 54.0% males. The maximum concentration of ciprofloxacin in aqueous humor observed was 0.47 ± 0.057 µg/ml at 0.83 h. While the maximum concentration with concurrent administration of ciprofloxacin with diclofenac sodium was 0.44 ± 0.00577 µg/ml at 0.25 h. Time to reach maximum concentration was decreased to 0.3 h. t_{1/2abs and} tα_1/2 were not significantly affected by co-administration of the ciprofloxacin eye drops with the diclofenac sodium eye drops (P = 0.73), however, t_1/2βwas significantly affected (P = 0.036). Similarly, apparent volume of distribution, volume of central compartment, steady-state distribution volume, AUC_0-t and MRT were also significantly reduced due to concurrent administration of the diclofenac sodium eye drops with the ciprofloxacin eye drops (P = 0.021, 0.0.017, 0.05, 0.01 and 0.04). On the other hand, the ocular Cl_t was significantly elevated (P = 0.04), while absorption rate constant (P = 0.58) was non significantly decreased due to concurrent administration of the diclofenac sodium eye drops, while C_max was not significantly affected. Diclofenac sodium affects the pharmacokinetics of ciprofloxacin when co-administered with ciprofloxacin eye drops.

Key words: Ciprofloxacin ophthalmic drops, pharmacokinetics drug-drug interaction, aqueous humor.