Susanne Gardner – [email protected] Luis Cordoves – [email protected] Ejaz Ansari – [email protected] special focus 11

contacts

DespiteINTRACAMERAL increases in dose administered, the subconjunctivalCEFUROXIME injection does not achieve aqueous humour levels comparable to the intracameral injection by Susanne Gardner D Pharm

Cefuroxime Moxifloxacin Vancomycin Dose AH level Dose AH level Dose AH level High antibiotic a b d f f “levels are achieved Topical drops 25mg 0.18-2.16 0.5% 2.28 50 mg/ml 2.04 (@50mg/ml) (@5mg/ml)d instantaneously after

a b e e g g intracameral injection, Subconjunctival 25mg 2.31-5.65 1 mg 3.03 20 mg 24.8 without delays due to injection 125 mga 20.23c drug diffusion

Intracameral 1 mgh 3300h injection Susanne Gardner D Pharm

Mean AH antibiotic levels (μg/ml) after various routes of administration intracameral cefuroxime at the end of (a) Adapted from reference 3. (b) Ref. 3: AH sampling times (12-24 minutes) - (120-160 minutes) after dose. (c) Ref. 3: AH sample at 12-24 minutes after dose. (d) Ref. 5: following Q2h topical drop dosing. surgery.8 (e) Ref. 4: Mean peak level measured at one hour post-dose. (f) Ref. 7: Two drops (one each about 20’ and 30’ before surgery). (g) Ref. 6: Measured at five hours post-dose. (h) Approximate AH concentration, it is important to recall that any extrapolated from intracameral 1mg dose, using anterior chamber volume of 0.3 ml discussion of measured ocular antibiotic levels implies correlation with bacterial ow does subconjunctival subconjunctival injection given at various MiCs and anticipated bactericidal effects injection compare with times prior to .4 Ah “...we strive to deliver over time. These “drug-bug” interactions intracameral injection or levels reached 3.03 μg/ml one hour after vary considerably with bacterial strain and topical drops in terms of the highest, safe, injection (see table), dropping to 1.91 μg/ antibiotic. however, because the eye does not pharmacokinetics?" ml at three hours; 0.53 μg/ml at five hours; "h lend itself to multiple intraocular entries, and This question is timely in the wake single antibiotic dose and 0.3 μg/ml at six hours post-dose. in corneal layers are an intended barrier to the of recent developments surrounding comparison, topical drops given Q2h before environment, we strive to deliver the highest, intracameral cefuroxime discussed whenever possible, so that surgery produced Ah levels of 2.28 μg/ml.5 safe, single antibiotic dose whenever possible, throughout this issue. The available subconjunctival vancomycin resulted in meaningful intraocular so that meaningful intraocular antibiotic data allow direct comparison of drug substantially higher Ah concentrations than levels are sustained for as long a period of levels achieved after subconjunctival vs. did topical drops, despite the use of a higher antibiotic levels are time as possible. To date, the intracameral intracameral injection. drop concentration (see table).6,7 injection remains the method of drug The subconjunctival injection places the sustained for as long a By direct injection into the anterior delivery that best accomplishes this goal. drug near the anterior surface of the eye, chamber, the intracameral injection forming a depot beneath the conjunctival period of time as possible” bypasses corneal and external ocular References barrier adjacent to the . Drug diffuses 25mg subconjunctival dose reached 5.65 barriers, and reduces interpatient variability into adjacent ocular structures, but the μg/ml, but only 2.16 μg/ml after a similar in the delivered dose. high antibiotic 1. Wine NA, Gornall AG, Basu PK. The ocular uptake of injection port itself is thought to facilitate levels are achieved instantaneously after subconjunctivally injected C14 hydrocortisone. I. Time and topical drop dose (see table). increasing major route of penetration in a normal eye. Am J Ophthalmol 1,2 leakage back into the conjunctival sac the subconjunctival dose to 125mg raised intracameral injection, without delays due 1964;58:362-366. bathing the external with injected Ah levels to 20.23 μg/ml at 12-24 minutes, to drug diffusion. The cefuroxime 1.0mg 2. Gardner SK. Ocular Drug Penetration and Pharmacokinetic solution. Penetration through corneal with levels still rising at the last sampling intracameral injection delivers Ah levels Principles. In: Lamberts DW, Potter DE, eds. Clinical Ophthalmic layers to the aqueous humour is dependent at least 100 times greater than the highest Pharmacology. Boston: Little Brown & Co; 1987:1-52. time. in study eyes with a 10mm corneal 3. Jenkins CDG, Tuft SJ, Sheraidah G, et al. Comparative on drug lipophilicity, hydrophilicity, and wound, topical 12.5mg cefuroxime produced subconjunctival dose (see table). intraocular penetration of topical and injected cefuroxime. molecular size, among other factors. in Ah peaks of 9.34 μg/ml at 12-24 minutes, Nevertheless, Ejaz Ansari FRCOphth, Br J Ophthalmol 1996;80:685-688. contrast to topical drops that introduce whereas the same dose to a normal cornea MD points out that some centres continue 4. Matsuura K. Pharmacokinetics of subconjunctival injection interpatient variability in retained dose, use of postoperative subconjunctival of moxifloxacin in humans. Graefes Arch Clin Exp produced lower levels of 0.05 μg/ml. Ophthalmol 2012. subconjunctival and intracameral injections The authors concluded that, in an intact because endophthalmitis 5. Hariprasad SM, Blinder KJ, Shah GK et al. Penetration deliver a known finite dose. eye, only the subconjunctival route of rates are perceived as relatively low and pharmacokinetics of topically administered 0.5% moxifloxacin administration produced Ah levels > 1 μg/ subconjunctival corticosteroids are also ophthalmic solution in human aqueous and vitreous. Arch Comparing ocular cefuroxime given. Luis Cordoves MD, of the hospital Ophthalmol 2005; 123:39-44. ml at 12-24 minutes post-dose, with levels 6. Souli M, Kopsinis G, Kavouklis E, et al. Vancomycin levels in levels after various routes of rising slowly over time after either drops or Universitario de Canarias, spain, however, human aqueous humour after intravenous and subconjunctival administration in 1996, Jenkins subconjunctival injection. Nevertheless, the finds that subconjunctival injection is administration. Int J Antimicrob Agents 2001;18:239-43. and associates3 measured anterior table shows that Ah cefuroxime levels after often painful with current modes of topical 7. Alster Y, Herlin L, Lazar M, Loewenstein A. Intraocular chamber cefuroxime concentrations anaesthesia, and emphasises that one penetration of vancomycin eye drops after application an intracameral injection exceed levels after to the medial canthus with closed lids. Br J Ophthalmol after administration routes that included subconjunctival injection, or after drops, study reported a three-fold reduction in 2000;84:300-302. subconjunctival injection and frequent even in the presence of a corneal wound. postoperative endophthalmitis rates after 8. Yu-Wai-Man P, Morgan SJ, Hildreth AJ, et al. Efficacy of topical drops. Mean aqueous humour (Ah) A more recent study examined 50mg subconjunctival cefuroxime was intracameral and subconjunctival cefuroxime in preventing cefuroxime levels 120-160 minutes after a discontinued, and replaced with 1.0mg endophthalmitis after cataract surgery. J Cataract Refract Surg Ah moxifloxacin levels after a 1.0mg 2008;34:447-451.

EUROTIMES | Volume 18 | Issue 3