강화된 Tobramycin 안용액의 점안시 가토각막내의 Tobramycin 농도에 관한 연구

Abstract

[한글]

안과영역에서 세균성각막염은 흔한 질환이며, 특히 녹농균성각막염의 경우에는 24-48시간내에 각막천공이 생기는 수가 있으므로 적절한 치료제를 빨리, 다량으로 투여하여야 한다.

현재 세균성각막염의 치료에 있어서 고농도와 aminoglycoside 계의 항생제 안용액이 강조되고 있으며, 1985년 Glasser등은 강화된 gentamicin 안용액을 가토에게 점안하여 gentamicin의 각막내 농도를 보고한 바 있다.

저자는 강화된 tobramycin안용액을 제조, 가토에게 점안하여, 눈에 해롭지 않고 최대의 양을 투여할 수 있는 tobramycin의 점안 방법과 회수 및 그때의 tobramycin의 각막내 농도를 알아보았다.

1. 염증성 반응을 조사한 결과, 매시간마다 1방울씩 점안한 1군과 매2시간마다 3방울씩 점안한 5군에서는 결막충혈을 거의 볼수 없었으나, 매30분마다 1방울씩 점안한 2군과 처음에만 부하요법(1분간격으로 1방울씩 5회 점안) 그후 매시간 1방울씩 점안한 4군에서는 경한 결막충혈을, 매시간 부하요법을 시행한 3군에서는 중등도의 결막충혈 및 결막부종을 관찰할수 있었다. 모든 군에서 각막 및 흥채상태는 정상이었다.

2. Tobramycin의 각막내 최고농도는 점안 1시간 후에는 3군이 1, 2군보다 월등히 높고, 2시간 후에는 3군이 1, 2, 5군보다 월등히 높으며, 4시간 후에는 3군이 1, 2, 4, 5군보다 월등히 높음을 알수 있다. 4시간 후의 최저농도에서는 1군과 5군사이에 유의한 차이는 없었다.

[영문]

Bacterial keratitis is a common ophthalmic disease. In certain cases of pseudomonas keratitis, the corneal perforation may occur within 24-48 hours of the onset. So suitable, massive antibiotics should be promptly used in these cases.

Intensive topical therapy with fortified aminoglycoside antibiotics is a current mainstay in the treatment of bacterial keratitis because of insufficient antibiotic concentrations may not to inhibit bacterial growth.

In 1985, Glasser and associates reported the effect of longer dosing intervals on corneal gentamicin levels with using topical fortified gentamicin solutions in rabbits.

We compared peak and trough antibiotic levels achieved in the rabbit cornea by various topical administrations of tobramycin which was prepared in a concentration of 13.6mg/ml by fortifying commercially available ophthalmic tobramycin solution with injectable drug. A loading dose consists of one drop given every minute for five minutes.

1. Eyes receiving one drop every hour (Group 1) and three drops every two hours (Group 5) showed little conjunctival hyperemia. Eyes given one drop every 30 minutes (Group 2) developed minimal inflammatory responses, as did eyes given a single loading dose followed by one drop each hour (Group 4). The moderate inflammatory response occurred in eyes receiving sequential leading doses (Group 3). Abnormalities in the cornea and the iris were not seen in all studied groups.

2. Gentamicin peak level in sequential loading doses group (Group 3) was significantly higher than those achieved by one droop every hour (Group 1) or one drop every 30 minutes (Group 2). At two hours of gentamicin administration, sequential leading doses (Group 3) produced remarkably high concentrations than those produced in Group 1, Group 2, or three drops every two hours (Group 5). During the first four hours, Group 3 represented high antibiotic levels than those produced in Group 1, Group 2, croup 5, or a single loading dose followed by one drop each hour (Group 4). There were no significant differences between trough

levels with one drop every hour (7roup 1) and three drops every two hours (Group 5).