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Characterization of Ocular Pharmacokinetics of Beta-Blockers Using a Diffusion Model After Instillation

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Abstract

Purpose. To characterize the ocular pharmacokinetics of beta-blockers (timolol and tilisolol) after instillation in the albino rabbit using a mathematical model that includes a diffusion process.

Methods. The disposition of fluorescein isothiocyanate-dextran (FITC-dextran, molecular weight 4400), timolol, and tilisolol was determined in tear fluid and aqueous humor after instillation or ocular injection in rabbits. The in vivo penetration parameters were estimated by fitting the concentration-time profiles to the Laplace equations based on a diffusion model using MULTI(FILT) program. Thein vivo permeability of drugs was measured across cornea using a two-chamber diffusion cell.

Results. Concentration-time profiles of drugs in the tear fluid after instillation showed a monoexponential curve. Although a monoexponential curve was observed in the aqueous humor concentration of FITC-dextran after injection into the aqueous chamber, timolol and tilisolol showed a biexponential curve. On the basis of these results, anin vivo pharmacokinetic model was developed for estimation of penetration parameters. The in vitro partition parameters were higher than those of the in vivo parameters.

Conclusions. The ocular absorption of timolol and tilisolol was characterized using an in vivo pharmacokinetic model and in vivo penetration parameters.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki City, Japan

    Kenzo Yamamura, Takahiro Mukai, Koyo Nishida & Junzo Nakamura

  2. Department of Hospital Pharmacy, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki City, Japan

    Hitoshi Sasaki, Mikiro Nakashima & Masataka Ichikawa

Authors
  1. Kenzo Yamamura
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  2. Hitoshi Sasaki
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  3. Mikiro Nakashima
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  4. Masataka Ichikawa
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  5. Takahiro Mukai
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  6. Koyo Nishida
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  7. Junzo Nakamura
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Correspondence to Hitoshi Sasaki.

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Yamamura, K., Sasaki, H., Nakashima, M. et al. Characterization of Ocular Pharmacokinetics of Beta-Blockers Using a Diffusion Model After Instillation. Pharm Res 16, 1596–1601 (1999). https://doi.org/10.1023/A:1018964823193

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