SCIENTIFIC CORRESPONDENCE Penetration of topical, oral, and combined administered ofloxacin into the subretinal fluid

Aims—To assess the subretinal fluid (SRF) levels of ofloxacin following topical, oral or combined administration. Methods—31 patients undergoing conventional retinal reattachment surgery were randomly assigned to three groups. Nine patients received topical ofloxacin, 11 patients received oral ofloxacin, and the other 11 patients received combined administration. Collected SRF samples were analysed for drug level by using high performance liquid chromatography. Results—SRF drug levels after oral and combined administration were significantly higher than that after topical administration (p=0.0002 and p=0.0002, respectively) while there was no significant diVerence between oral and combined administration (p=0.0844). Conclusions—Ocular bioavailability of ofloxacin in SRF after oral and combined administration is equivalent. The addition of oral ofloxacin to topical therapy increased drug SRF penetration sixfold. (Br J Ophthalmol 1999;83:1183–1185) Ofloxacin is a fluoroquinolone antibiotic with rapid bactericidal activity interfering with DNA gyrase of bacteria. It has a high oral bioavailability and excellent tissue penetration. 2 Its favourable pharmacokinetic properties also make it useful in ophthalmic infections in the form of a topical 0.3% solution. Penetration of topical, systemic, or combined ofloxacin into cornea, aqueous, and vitreous humour has already been studied. However, no published result was found with regard the subretinal fluid (SRF) level of the drug. The aim of this study was to determine the SRF concentration of ofloxacin following diVerent type of applications by using a sensitive and reliable method described by Basci et al. Materials and methods Thirty one patients undergoing conventional retinal reattachment surgery were selected for the study. Nine patients (mean age 38.5 years; five male and four female), starting 6 hours before surgery, received 2 drops of 0.3% ofloxacin solution every 30 minutes for the first 3 hours and hourly instillation for the next 3 hours. Eleven patients (mean age 40.5 years; six male and five female) received a single oral dose of 400 mg ofloxacin 8 hours before surgery. The other 11 patients (mean age 37 years, five male and six female) received a combination of those applications. Drug administration was done by a nurse to ensure compliance. SRF samples were obtained as described by Lesk et al 15 at the sclerotomy drainage site. Samples were stored immediately in a freezer at −70°C. All the patients had a uninflammed cornea, intact crystalline lens, and posterior capsule. Exclusion criteria included the presence of a fresh vitreous haemorrhage, age less than 18 years, pregnancy, diabetes mellitus, topical or systemic antibiotic or any drug that may interfere with ofloxacin use during 1 week before enrolment, allergy to quinolones, history of central nervous system, renal, or hepatic diseases. Written informed consent was obtained from each patient, and the study was approved by the ethics committee of SSK Ankara Eye Hospital, Ankara, Turkey. High performance liquid chromatography (HPLC) grade methanol and acetonitrile were obtained from J T Baker (Phillipsburg, NJ, USA) and analytical grade citric acid and pipemidic acid from Sigma (St Louis, MO, USA). The ophthalmic solution of ofloxacin used contained benzalkonium chloride (0.005%), hydrochloric acid, sodium hydroxide (pH approximately 6.4), and sterile water as inactive ingredients. Stock solutions of ofloxacin (1 mg/ml) and pipemidic acid (1 mg/ml) were prepared in hydrochloric acid (0.01 N) and sodium hydroxide (0.2 M), respectively. Standard solutions of ofloxacin containing pipemidic acid (1 μg/ml) were prepared as internal standard by diluting the stock solutions of ofloxacin. Ofloxacin was measured by using an HPLC method that involves direct injection of the samples. The chromatography system consisted of a Varian 9002 solvent delivery system (Varian Associates Inc, Lexington, MA, USA), Varian 9100 autosampler, Waters 470 scanning fluorescence detector (Waters Chromatography, Milford, MA, USA), and Waters 746 data Br J Ophthalmol 1999;83:1183–1185 1183 SSK Ankara Eye Hospital, Department of Vitreoretinal Surgery, Ankara, Turkey