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ORIGINAL ARTICLE
Year : 1983  |  Volume : 31  |  Issue : 4  |  Page : 447-449
 

"Estimation of trimethoprim and sulfamethoxazole levels in tears after systemic administration"


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G K Sharma
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How to cite this article:
Sharma G K, Kabra S G, Garg R P, Sharma P K, Nepalia L K. "Estimation of trimethoprim and sulfamethoxazole levels in tears after systemic administration". Indian J Ophthalmol 1983;31:447-9

How to cite this URL:
Sharma G K, Kabra S G, Garg R P, Sharma P K, Nepalia L K. "Estimation of trimethoprim and sulfamethoxazole levels in tears after systemic administration". Indian J Ophthalmol [serial online] 1983 [cited 2014 Oct 24];31:447-9. Available from: http://www.ijo.in/text.asp?1983/31/4/447/27576


The control of ophthalmic infection still remains a challange. Though rationally spaced topical instillations work in most of the cases, yet systemic administration enjoys advantage of acting internally through blood and externally through tears provided the drug is excreted in adequate concentration in kears. Further, a drug secreted in tears has more sustained effect than the locallay instil­led one, which tends to be flushed out.

Trimethoprim and Sulfamethoxazole combination is presently used widely as a mutually potentiating antibacterial combina­tion at minimum inhibitory concentration in blood[1],[2]. Their penetration in various body fluids has been assessed by several workers. However, its analysis in tears seems to have been conspicuously neglected. Hence it was considered pertinent to evaluate the concen­

tration of Trimethoprim and Sulfamethoxa zole in tears.


  Materials and methods Top


Subject matterof the present study compri­sed of 50 normals of either sex and varying age. They were given 160 mg. of Trimethoprim and 800 mg. of Sulfamethoxazole 12 hourly in 5 groups of 10 individuals each varying from groups to 10 dosage. The samples 0.5 ml. of tear and 2 ml. of blood were taken simultaneously every 4 hours for 12 hours, after the last dose, for the estimation of drug in them by colorimetric method of Shepered[3] for Trimethoprim and colorimetric method of Deniel[4] for Sulfamethoxazole.


  Observations Top


The levels of Trimethoprim and Sulfame­thoxazole in tears at various hours are presented in [Table - 1] and 2 respectively.


  Discussions Top


The concentrations of Trimethoprim and Sulfamethoxazole estimated in tears and plasma in the present study are more than the minimum inhibitory concentration values for most of the sensitive organisms[5]. In inflammatory conditions, the concentration of these drugs in tears is expected to be still higher due to increase in permeability of the inflammed tissues.

On estimation of Trimethoprim and Sulfamethoxazole concentration in plasma and tears, it was observed that the maximum concentration of these drugs was achieved in (1 to 10 dosage). The rise in level was more significant in case of Sulfamethoxazole than Trimethoprim which can be due to the cumulative effect in case of Sulfamethoxazole. However, in case of Trimethoprim the increasing levels were due to alkalinising the urine which decreased its clearance[6].

Statistical analysis of the observations presented revealed a highly significant (p L.0.001) positive correlation between the serum and tear levels of Trimethoprim and Sulfamethoxazole at various dose intervals as shown below:



4 hours, followed by a decline at 8 and 12 hours. An ever increasing rise in concentra­tion of both the drugs was observed in plasma and tears on increasing dosage schedule

Both the drugs were secreted in tears and their levels in Vsub tears bore a statistically significant correlation (r= -+ 0.77, r= +0.76) with the serum level. The tear concentration of Trimethoprim was significantly (p 40.001) greater than the serum level and consistently correlated with cumulative serum level pro­gressively from 1 to 10 dosage administra­tions. Similar higher levels in other body fluids than in plasma have been reported in sputum and saliva[7] and in prostatic secre­tions[8]. It may be because of a dual process of ultrafiltration and active transport that steps up the Trimethoprim level in tears. The level of Sulfamethoxazole in tear however was consistently lower than the serum level.

It is therefore concluded that systemic administration of a commonly used combi­nation of Trimethoprim and Sulfamethoxa­zole is a useful adjunct in the treatment of ophthalmic infections especially corneal ulcer and acute bacterial conjunctivitis. Trime­thoprim because of its demonstrated selective concentration in tears is likely to be more effective and beneficial.


  Summary Top


50 normals were studied for the Trime­thoprim and Sulfamethoxazole levels in plasma and tears. It was observed that both the drugs are secreted in tears in statistically significant concentration higher than the minimum inhibitory concentration for most of the organisms. The concentration in tear is dependent upon plasma concentration which in turn is dose dependent. Trimetho­prim is selectivily and actively secreted in tear. Hence systemic administration of Trimethoprim and Sulfamethoxazole is a useful adjunct to topical instillations.

 
  References Top

1.Hitchings, G.H. and Burchall, J.J., 1965 Molec. Pharmacol. 1, 126: 136. cited by Bushby, et al. 1968 Birt. J. Pharmacol. 33, 72-90.  Back to cited text no. 1    
2.Darrel, J.H., Garod. L.P., and waterworth, Pamela M. 1968 J. of Clinical Pathology, 21: 202.  Back to cited text no. 2    
3.Shepered, R.G., 1948 Ant, Chem. 20,: 1150.   Back to cited text no. 3    
4.Daniel., J.W., 1961 Analyst, 86, 640.  Back to cited text no. 4    
5.Bushby, S.R.M. 1969 Postgrad, Med. J. 45, 10-17.  Back to cited text no. 5    
6.Sharpstone, P. 1969 Postrad, Med. J. 45, suppl., 38.  Back to cited text no. 6    
7.Hughes, B.T.D., Bye, A., and Hedde., P. 1971 Proc. 7th Int. Congr. Chemother. 1, 1105.  Back to cited text no. 7    
8.Neilsen. M.L. and Hansen Th. 1972 Scand. J. Urol. Nephrol. 6, 245.  Back to cited text no. 8    


    Tables

[Table - 1], [Table - 2]



 

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