Improved penetration of aminoglycosides and fluorozuinolones into the aqueous humour of patients by means of Acuvue contact lenses.
OBJECTIVE
In order to improve the penetration of topically applied drugs in ophthalmology, the suitability of hydrophilic contact lenses (Acuvue, Vistacon, power -1.0 D) as a drug delivery system for antibiotics was tested. A prospective study was undertaken to determine the transcorneal penetration of five topically applied aminoglycosides and fluoroquinolones into the aqueous humour of patients.


METHODS
Two hundred and sixty-five patients undergoing cataract extraction received 0.3% gentamicin, kanamycin, tobramycin, ciprofloxacin or ofloxacin solution by two different modes of administration: either as eye drops (nine drops every 15 min, starting 2 h prior to surgery) or by means of a drug delivery system (Acuvue contact lenses soaked for 1 h in eye drop solution without preservatives, 15 h prior to surgery). At the beginning of cataract extraction, 50-100 microl aqueous fluid was aspirated from the anterior chamber and immediately stored at -80 degrees C. Antibiotic concentrations were measured using fluorescence polarisation immunoassays (aminoglycosides) or high-performance liquid chromatography (fluoroquinolones).


RESULTS
After soaking for 1h in 0.3% eye drop solutions, Acuvue contact lenses released about 190-250 microg aminoglycoside and ofloxacin and 1000 microg ciprofloxacin. These amounts are considerably lower or in the same order of magnitude than obtained with application of eye drops (1350 microg). From the aminoglycosides tested, only gentamicin and tobramycin, but not kanamycin, were able to penetrate into the aqueous humour of patients. After the wearing of antibiotic-soaked lenses, mean aqueous humour concentrations were higher than after the use of eye drops. This difference reached significance in tobramycin (1.09 (1.30) microg x ml(-1) vs 0.49 (0.79) microg x ml(-1)), ciprofloxacin (1.23 (0.60) microg x ml(-1) vs 0.38 (0.33) microg x ml(-1)) and ofloxacin (5.55 (2.53) microg x ml(-1) vs 0.56 (0.37) microg x ml(-1)). The percentage of patients with aqueous humour concentration above the MIC90 of Staphylococcus epidermidis, the most common cause of postoperative endophthalmitis, was 92% and 100% after wearing ciprofloxacin- or ofloxacin-soaked lenses, respectively.


CONCLUSIONS
Gentamicin and tobramycin penetrated into the aqueous humour of patients, whereas kanamycin was not able to overcome the corneal barrier. Acuvue contact lenses soaked in 0.3% eye drop solutions can release sufficient amounts of gentamicin, ciprofloxacin and ofloxacin to produce bacteriostatic concentrations in the humor aquosus. Acuvue contact lenses can be recommended as a drug delivery system for fluoroquinolones.
Hehl
E M
EM
Institute of Experimental and Clinical Pharmacology and Toxicology, Deparment of Clinical Pharmacology, University of Rostock, Germany.
Beck
R
R
Luthard
K
K
Guthoff
R
R
Drewelow
B
B
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D003263:Contact Lenses, Hydrophilic; D016503:Drug Delivery Systems; D015817:Eye Infections / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007612:Kanamycin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D009883:Ophthalmic Solutions; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014031:Tobramycin / Q000008:administration & dosage / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D005839:Gentamicins; D009883:Ophthalmic Solutions; D007612:Kanamycin; D002939:Ciprofloxacin; D015242:Ofloxacin; D014031:Tobramycin