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Year : 1981  |  Volume : 29  |  Issue : 3  |  Page : 307-311

Gentamicin penetration in human aqueous after subconjunctival injection

Department of Ophthalmology R.N.T. Medical College, Udaipur, India

Correspondence Address:
M R Jain
Department of Ophthalmology R.N.T. Medical College, Udaipur
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Source of Support: None, Conflict of Interest: None

PMID: 7346450

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How to cite this article:
Jain M R, Bansal V D. Gentamicin penetration in human aqueous after subconjunctival injection. Indian J Ophthalmol 1981;29:307-11

How to cite this URL:
Jain M R, Bansal V D. Gentamicin penetration in human aqueous after subconjunctival injection. Indian J Ophthalmol [serial online] 1981 [cited 2023 Dec 1];29:307-11. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1981/29/3/307/30908

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Table 1

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Table 1

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Gentamicin is a water soluble aminoglyco­side derieved from Micromonospora purpurea, an actinomycete. It is a wide spectrum anti­biotic effective against a wide range of grain positive and gram negative organisms, especi­ally S. aureus, most Proteus species, 95 percent of P. aeruginosa and other Entero­bacteriaceae.

Gentamicin exerts antibacterial activity by inhibition of bacterial protein synthesis-RNA mesenger. It's optimum effect is noted in alkaline PH and inhibitary concentrations for sensitive organisms vary between 5 and 10 ug/ml.

The present study is designed to study the penetration of gentamicin in human aqueous in relation to time with an aim to determine the time of its peak penetration and the period of its availability in aqueous after a subcon­junctival injection in therapeutic doses.

  Materials and methods Top

90 healthy patients with uncomplicated senile cataracts admitted to eye ward for cataract operation, were the subject of this study, No local or systemic antibiotic of any type was used before collecting aqueous samples. Each case was injected 20 mg, of gentamicin sulphate (GENTICYN) dissolved in 0.5 ml. of distilled water, subconjunctivally in the lower fornix. The injection was given at such a time so as to plan a stipulated time interval at the time of cataract operation. The dose to sample interval varied from ¼,½, 1, 2, 4, 6, 8, and 12 hours in groups of 10 cases each and 18 and 24 hours in group of 5 cases each.

0.08 to 0.2 ml. of aqueous was aspirated with a tuberculin syringe after placing an oblique corneal incision at the time of cataract surgery.

For estimation of gentamicin concentration, a modified disc diffusion method using medium No. 5 of Grove and Randall availa­ble as Difco antibiotic medium, adjusted to PH of 8.0 ± 0.1 with NaOH, was used. Organisms used were suspension of spores of B. Subtilis NCIM 2063 grown on heart in­fusion agar in Roux bottles.

Standard Whatman filter paper No. 1 discs of gentamicin sulphate with concentrations of 20, 10, 5, 2, 5 and 1.25 ug/ml and discs soaked in aspirated samples were placed in the medium and the zone of inhibition measu­red with a vernier microscope and plotted on a semilog paper.

  Observations Top

Mean age in the group was 56.4 years with a range of 45 to 70 years. Maximum number of cases belonged to the age group of 55 to 64 years. Male and female ratio was 5.3 : 3.7.

[Figure - 1] and [Table - 1] show that the drug enters into aqueous shortly after injection showing mean concentration of 3.53 ± 2.704 ug/ml in the samples collected 15 minutes after the injection and the drug attains maximum concentration of 14.82 ± 8.504 ug/ml. within one hour. Drug penetrate gradually upto 12 hours (6.64 ± 2.19 ug/ml.) and thereafter, the samples collected at 18 hours interval show concentration of 1.12 + 0.374 ug/ml. None of the samples at 24 hours interval show the presence of the drug.

  Discussion Top

The rationale of absorption of the drug into the eye after subconjunctival injection is explained on the basis of diffusion through the sclera, since the sclera allows free and indis­criminate passage of water soluble drugs even with big molecular size. Gentamicin sulphate is highly water soluble having better diffusion and better tolerance due to its low osmotic pressure as compared to other antibiotics[2].

[Table - 2] shows values of comparative con­centration of gentamicin penetration into the eyes in various studies conducted till date. In addition to the largest number of subjects employed by us, we utilized uniform dose of 20 mg in all cases and conducted estimation at various time intervals, extending from hour to 24 hours. Maximum mean concen­tration noted by us was 14.82 ug/ml at 1 hour interval, whereas, in rabbits, Litwack et al(5) noted maximum mean concentration of 16.3 ug/ml at 1 hour interval. In the studies con­ducted in human beings by Furgiuele[1] and Methalone and Harden(6) with doses of 10 and 20 mg., the concentration noted was 4.8 & 6.7 ug/ml respectively. Higher concentration of 15.6 ug/ml. was observed by Methalone and Harden(6) when the dose was raised to 80 mg but the drug when utilized in such high sub­conjunctival doses, is reported to be absorbed in serum in the concentration of 0.80 ug/ml and may cause local and systemic side effects(6). None of the earlier worker has conducted estimation study for long intervals. Our results established that the drug attains a significantly high concentration of 3.53 ± 2.704 ug/ml within 15 minutes of injection and shoots upto its maximum within 1 hour and thereafter declines till at 18 hours interval the drug concentration is 1.12 ± 374 ug/ml. Twenty four hours samples show complete absence of drug.

Most interesting conclusions can be deri­ved when our results are compared to that of Jain & Singhal[4] and Jain & Modi[3] where they studied intraocular penetration of Chloromycetin and carbenicillin respectively. These two studies have also been conducted in a large series of cases with limited age range of 45 to 70 years, with uniform dosage and at various time intervals. [Figure - 2] shows comparative concentration of drug penetration as regards intensity and duration. It also shows as to how long the M.I.C. concentration of a particular antibiotic persists in the aqueous against the common ocular pathogens, namely­ Staphylococcus aureus, pseudomonas aerugi­nosa and E. coli, All the three drugs attain effective concentration against staphyloccus aureus and E. Coli but against pseudomonas aerugenosa, gentamicin & carbenicillin only attains effective concentration. The duration of effective concentration of gentamicin for all the three organisms persists for considera­bly longer duration than that of other two antibiotics.

It can further be derived from the above figure that gentamicin maintains bactericidal concentration of more than 10 ug/ml for sensitive organisms for at least a period of 5 hours i.e. 1st hour to 6th hour. Litwack et al(5) noted than 98 percent of clinically isolated 46 strains of ps. aerugenosa were affected with 3.12 ug/ml. of gentamicin and a concentration of 12.5 ug/ml. inhibited 100 percent strains of pseudomonas aerugenosa. Hence, it can be concluded that a single subconjunctival injection of 20 mg. of genta­micin becomes effective within 15 minutes against 98 percent ps. aeruginosa and this effectiveness is maintained at least for 12 hours. During the interval of I to 2 hours, the drug is able to inhibit 100 percent strains.

Tolerance of the drug was extremely good. Chemosis and irritation of conjunctival was minimal and much less as compared to neomy­cin, bacitracin, and polymyxin[2]. Chloromyce­tin and carbencillin too showed comparatively more chemosis and irritation. None of our cases complained of acute pain or severe discomfort.

  Summary Top

In 90 human eyes, gentamicin sulphate has been estimated in aqueous by microassay, utilizing disc deffusion technique. 20 mg. of gentamicin sulphate (GENTICYN-Indian Schering) was injected subconjunctivally and the cases were divided into 10 groups depen­ding upon dose to sample interval i.e. ¼ to 24 hours. Significant drug concentration was noted within 15 minutes of injection. It reached to its peak level of 14.82 ± 8.504 ug/ml within one hour. Drug could be detec­ted upto 18 hours but 24 hours samples were devoid of the drug. It was concluded that with a single sub-conjunctiva l injection aqueous concentration attained was sufficient to kill all the commonly occurring ocular pathogens, including 100 percent strains of ps. aeruginosa.

  References Top

Furgiuele, F.P. 1970, Am. J. Ophthalmol., 69: 481.  Back to cited text no. 1
Goulstine, D.B. and Marmion, V.J., 1972, Brit. J. Ophthalmol. 55 : 478.  Back to cited text no. 2
Litwack, K.D., petit, T.H. and Johnson, B.L., 1969, Arch. Opththalmol., 82 : 687.  Back to cited text no. 3
Mathalone, M.B.R. and Harden, A., 1972, Brit. J. Ophthalmol, 56 : 609.  Back to cited text no. 4


  [Figure - 1], [Figure - 2]

  [Table - 1], [Table - 2]


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