Ocular Pharmacokinetics

Maurice, David M.; Mishima, S

doi:10.1007/978-3-642-69222-2_2

Cited by 224 publications

(174 citation statements)

References 244 publications

(182 reference statements)

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“…Most studies simply describe drug penetration in the eye to determine whether therapeutic concentrations are achieved. While composite data from different subjects are occasionally pooled (11,21,23,36), this approach to pharmacokinetic analysis is limited because of intersubject variation (33). Penetration of many antibiotics is marginal following systemic drug administra1Op- 10 Ie tion.…”

Section: Discussionmentioning

confidence: 99%

“…In rabbits, the elimination of fleroxacin is more rapid than that in humans because of the increased metabolism and active tubular secretion which is blocked by probenecid (20,34). Rapid entry and elimination of fleroxacin in the vitreous humor indicates that elimination occurs through the retina (23).…”

Section: Discussionmentioning

confidence: 99%

“…Kinetic constants from each animal were then combined to generate population data (2,21,23,26). Ocular and serum pharmacokinetics were compared.…”

mentioning

confidence: 99%

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

Miller

Madu

Samathanam

et al. 1992

Antimicrob Agents Chemother

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Miller

Madu

Samathanam

et al. 1992

Antimicrob Agents Chemother

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“…D'un point de vue pharmacocinétique, l'oeil est considéré comme séparé du reste de l'organisme, le passage systémique d'un produit administré dans l'oeil étant quantitativement négligeable. Une modélisation pharmacocinétique propre au segment antérieur est utilisée [9]. Pour le segment postérieur, aucune modélisation pharmacocinétique n'a pu être établie [10].…”

Section: L'oeil Un Organe Isolé De La Circulation Par Des Barrièresunclassified

“…L'injection intravitréenne est de plus en plus utilisée. Un produit injecté dans le vitré est éliminé en deux à 18 heures, soit par diffusion antérieure vers l'humeur aqueuse, soit par diffusion transrétinienne vers la choroïde [9,13,14]. Des formulations peu solubles peuvent avoir un effet plus prolongé (Kénacort ® ).…”

Section: L'oeil Un Organe Isolé De La Circulation Par Des Barrièresunclassified

Vectorisation intra-oculaire

Behar-Cohen

2004

Med Sci (Paris)

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Face aux progrès considérables en chirurgie ophtalmologique, le traitement médical des maladies oculaires a peu évolué. L'instillation de collyres reste la méthode théra-peutique la plus employée, mais elle est inefficace dans le traitement des maladies rétiniennes. L'émergence de la thermothérapie transpupillaire [1] L'oeil, un organe isolé de la circulation par des barrièresLa rétine, extension du système nerveux central, tapisse la face interne et postérieure du globe oculaire. Les échanges entre la rétine et la circulation générale se font à travers deux barrières: la barrière hématorétinienne interne, composée de capillaires rétiniens non fenêtrés; la barrière hématorétinienne externe, composée de l'épi-thélium pigmenté à jonctions serrées. La rétine interne est ainsi vascularisée par un système capillaire hautement sélectif. La rétine externe, contenant les photoré-cepteurs, est avasculaire, nourrie par la choroïde au travers de l'épithélium pigmenté. Du fait de ces barrières, la biodisponibilité d'un produit administré par voie géné-rale est faible, sauf si le patient est soumis à des perfusions massives (pulse thérapie) ou s'il existe une rupture des barrières hémato-oculaires (inflammation). D'un point de vue pharmacocinétique, l'oeil est considéré comme séparé du reste de l'organisme, le passage systémique d'un produit administré dans l'oeil étant quantitativement négligeable. Une modélisation pharmacocinétique propre au segment antérieur est utilisée [9]. Pour le segment postérieur, aucune modélisation pharmacocinétique n'a pu être établie [10].

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A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application

Einmahl

Behar‐Cohen

Tabatabay

et al. 2000

J. Biomed. Mater. Res.

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The biocompatibility of a viscous, hydrophobic, bioerodible poly(ortho ester) (POE) intended for intraocular application was investigated. POE was evaluated as a blank carrier and as containing modulators of degradation. Each formulation was injected intracamerally and intravitreally in rabbit eyes, and clinical and histological examinations were performed postoperatively for 2 weeks. In the case of intracameral injections, polymer biocompatibility appeared to depend on the amount injected in the anterior chamber. When 50 microL was administered, the polymer degraded within 2 weeks, and clinical observations showed good biocompatibility of POE with no toxicity to the ocular tissues or increase in intraocular pressure. The injection of a larger volume, 100 microL, of POE, appeared inappropriate because of direct contact of polymeric material with the corneal endothelium, and triggered reversible edema and inflammation in the anterior chamber of the eye that regressed after a few days. After intravitreal administration, POE was well tolerated and no inflammatory reaction developed during the observation period. The polymer degraded slowly, appearing as a round whitish bubble in the vitreous cavity. The presence of modulators of degradation both improved POE biocompatibility and prolonged polymer lifetime in the eye. POE appears to be a promising biomaterial for clinical intraocular application.

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Ocular Pharmacokinetics

Cited by 224 publications

References 244 publications

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

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

Vectorisation intra-oculaire

A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application

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