Joomi Lee, Boram Ohk, Sook-Jin Seong, Mi-Ri Gwon, Hae Won Lee, Seunghoon Han, Young-Ran Yoon
Clinical Trial Center, Department of Biomedical Science and BK21 plus program, Kyungpook National University Hospital and School, Daegu, Korea
Background: The fourth-generation fluoroquinolone moxifloxacin is currently one of the antibiotic agents of choice for cataract surgery in most countries. Because it is difficult to obtain the concentration of moxifloxacin in human aqueous humor, the pharmacokinetic (PK) modeling of moxifloxacin has been rarely reported. The purpose of this study was to develop a population PK model to facilitate the understanding of the pharmacokinetics of moxifloxacin in human aqueous humor of patients undergoing cataract surgery after topical ocular administration of moxifloxacin hydrochloride ophthalmic solution 0.5%.
Methods: In 37 patients scheduled for cataract surgery, one drop of 0.5% moxifloxacin hydrochloride was topically administered 4 times a day on the preceding day and 4 times (q15min) for one hour right before surgery. Aqueous sample was collected 0.25 hour after the final dose. The concentration was determined using a validated liquid chromatography with tandem mass spectrometry method. A population PK analysis was performed using nonlinear mixed-effects modeling (NONMEM, Ver.7.1). Because of the insufficient data from our study, the dataset were generated for PK modeling from those presented in a published reference, using a statistical software package R (Ver. 2.11.1). The aqueous maximum concentration (Cmax): minimum inhibitory concentration for 50% of isolates (MIC50) values were calculated to predict successful bacteriologic response to moxifloxacin and the resultant clinical efficacy.
Results: A one-compartment disposition model with first-order absorption described the best fit to a total of 1000 generated dataset. The population parameter estimates for clearance, central volume, and absorption rate constant were 0.57 L h-1, 0.66 L, and 0.51 h-1, respectively. Through this PK model developed, the predicted PK parameters from 37 patients were obtained, and compared with the reference values. The mean Cmax/MIC50 value in our study was 26, which was consistent with that reported in the reference.
Conclusions: The population PK model developed adequately described the data observed in human aqueous humor after topical ocular administration of moxifloxacin. The developed model could be useful to optimize dosing regimen for topical prophylaxis before intraocular surgery.
References:
[1] Katz HR1, Masket S, Lane SS, et al. Absorption of topical moxifloxacin ophthalmic solution into human aqueous humor. Cornea. 2005 Nov;24(8):955-8.
[2] Mather R1, Karenchak LM, Romanowski EG, et al. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002 Apr;133(4):463-6.
This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2013R1A1A2060131).
Reference: PAGE 24 () Abstr 3641 [www.page-meeting.org/?abstract=3641]
Poster: Drug/Disease modeling - CNS