Abstract
Purpose :
To investigate the ocular pharmacokinetics and distribution of gatifloxacin between continuous lavage through the Morgan Lens and hourly topical drop instillation in New Zealand white rabbits using a simplified liquid chromatograph coupled with tandem mass spectrometry (LC-MS/MS).
Methods :
36 healthy rabbits were randomly divided into 2 groups. 0.3% gatifloxacin ophthalmic solution was instilled by either continuous lavage using Morgan Lens into the left eyes at 15 ml/h or 50 μL of the same solution administered topically every hour. The animals were sacrificed at 2, 4, 8, 12 h in the Morgan lens group or at 12, 24 h in the topical instillation group. Cornea, sclera and plasma specimens were collected. Pharmacokinetic and pharmacodynamics (PK/PD) indices, other than minimum inhibitory concentration (MIC), were used as therapeutic parameters in solid ocular tissues.
Results :
The concentration of gatifloxacin in the ocular tissues was much higher than that of the plasma, and the highest concentration were found in cornea in both groups. With continuous lavage, gatifloxacin reached high concentration in 2 hours in cornea, equivalent to about 10 times the concentration reached in same tissue by hourly topical instillation for 12 to 24 hours. Using historic data as references, for resistant Pseudomonas strains, the values of Cmax/MIC90 was 51(>10)and AUC/MIC90 417.7(>125)in cornea in the continuous lavage group, while 0.14 and 1.43 for the topical hourly instillation group.
Conclusions :
Compared to hourly topical instillation in our study, continuous lavage through the Morgan Lens achieved significant high concentration in ocular tissues within a short time, especially in cornea. Continuous lavage is a much more efficient way to treat recalcitrant corneal infections.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.