Fleroxacin pharmacokinetics in aqueous and vitreous humors determined by using complete concentration-time data from individual rabbits

Abstract

Although composite data from separate subjects can be used to generate single-subject estimates, intersubject variation precludes rigorous ocular pharmacokinetic analysis. Therefore, a rabbit model in which sequential aqueous and vitreous humor samples were obtained following the administration of the quinolone fleroxacin was developed. Mean data from individual animals were used for pharmacokinetic analysis. Following direct intravitreal or systemic drug administration, sequential paracenteses did not alter pharmacokinetic constants or ocular penetration and were not associated with an increase in ocular protein; contamination of vitreous humor with blood was minimal (<0.1%). Following direct injection or intravenous administration, vitreous humor concentration-time data were best described by one-and two-compartment models, respectively. The maximum concentration and the penetration into the aqueous and vitreous humors were 1.54 and 0.5 ,ug/ml and 27 and 10%, respectively. Elimination rates from aqueous and vitreous humors and serum were similar following parenteral drug administration. Drug elimination following direct injection was rapid, and the elimination rate from the vitreous humor was not prolonged by the coadministration of probenecid. Our animal model provides a new approach to the rigorous examination of the ocular pharmacokinetics of quinolone antimicrobial agents in the eye.

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography

“…Both in vitro and in animal models, fleroxacin's anti-gram-negative-bacterium activity has been shown to be comparable to that of the earlier fluoroquinolones (norfloxacin, pefloxacin, ciprofloxacin, and ofloxacin) (1,2,7,11,13,19,29,36,37,40). In addition, however, studies in endocarditis models, as well as in vitro, have shown that fleroxacin has significant activity against both methicillin-susceptible and -resistant Staphylococcus aureus (1,6,25,28).…”

Positively Charged Polymeric Nanoparticle Reservoirs of Terbinafine Hydrochloride: Preclinical Implications for Controlled Drug Delivery in the Aqueous Humor of Rabbits

“…As previously reported, this approach has an advantage of maintaining the integrity of the rabbits , corneas and the anterior chamber volume. When used to study the ocular pharmacokinetics in humans, it yields inaccurate and imprecise estimates because of inter-and intrasubject variations (45). The second technique involves a sequential sampling of the aqueous humor from the same rabbits.…”

Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits

“…By comparing pigmentation, dose mode, and elimination from vitreous humor, the vitreous humor half-life value for singly dosed albino rabbits (3.21 h) was not more rapid than that for singly dosed pigmented rabbits (4.32 h [P > 0.10]) but was more rapid than that for multiply dosed pigmented rabbits (6.05 h [P < 0.05]). The excellent penetration of ofloxacin into uninflamed rabbit eyes in conjunction with the higher levels in blood found in humans and greater activity against coagulase-negative staphylococci suggest that ofloxacin may be preferable to other quinolones for evaluation in the prophylaxis and treatment of bacterial endophthalmitis.We have recently developed and validated an ocular pharmacokinetic animal model which differs from conventional methods that obtain a single sample of vitreous humor from different animals (20,25,26,29). In our model, serial samples are obtained from the vitreous humor after intravenous drug administration.…”

“…We have recently developed and validated an ocular pharmacokinetic animal model which differs from conventional methods that obtain a single sample of vitreous humor from different animals (20,25,26,29). In our model, serial samples are obtained from the vitreous humor after intravenous drug administration.…”

“…In our model, serial samples are obtained from the vitreous humor after intravenous drug administration. This model does not alter the pharmacokinetics of drugs in the eye (24,25,29). Serial sampling is preferable, since it permits more-rigorous pharmacokinetic analysis and decreases the number of animals which are needed for the same degree of certainty in the pharmacokinetics parameter estimates by more than 50-fold compared with the single-sample approach (20).…”