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Antimicrobial Agents and Chemotherapy, June 2000, p. 1674-1679, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Pharmacokinetics of Ciprofloxacin in the Human Eye: a Clinical Study and Population Pharmacokinetic Analysis

Nigel Morlet,1,* Garry G. Graham,2 Barrie Gatus,3 Andrew J. McLachlan,4 Chris Salonikas,5 Daya Naidoo,5 Ivan Goldberg,1 and Chi Man Lam1

Departments of Ophthalmology,1 Microbiology,3 and Clinical Biochemistry,5 Prince of Wales Hospital, School of Physiology and Pharmacology, University of New South Wales,2 and Faculty of Pharmacy, University of Sydney,4 Sydney, New South Wales, Australia

Received 11 May 1999/Returned for modification 7 November 1999/Accepted 28 January 2000

Ciprofloxacin, a fluoroquinolone antibiotic active against a wide variety of bacteria, is one of a few antibiotics which enters the human eye after oral administration. However, little is known about its pharmacokinetics in the human eye. One or two oral doses of 750 mg of ciprofloxacin (at a 12-h interval) were administered to 48 patients at various times prior to ocular surgery. Clotted blood, aqueous, and vitreous were collected at surgery, and the concentrations of ciprofloxacin were assayed by high-performance liquid chromatography. Our data were combined with those of others, and a population pharmacokinetic analysis was conducted. The concentrations of ciprofloxacin in both aqueous and vitreous were lower than those in serum and peaked at a later time. The pharmacokinetics of ciprofloxacin in aqueous and vitreous were fitted to a compartmental model in which the antibiotic was transferred into and out of the two compartments (aqueous and vitreous) by first-order processes. Population pharmacokinetic software, P-Pharm, was used to calculate the mean half-lives of the loss of ciprofloxacin from aqueous and vitreous, which were 3.5 and 5.3 h, respectively. At steady state, the mean ratios of then concentrations in aqueous and vitreous to the concentrations in serum were 23 and 17%, respectively. After the administration of one or two doses of 750 mg of ciprofloxacin, the concentrations in both aqueous and vitreous in a number of patients were lower than the MICs at which 90% of isolates are inhibited (0.5 mg/liter) for common intraocular bacterial pathogens. Simulations of concentrations in the eye after the administration of higher doses (1,500 mg of ciprofloxacin as a single dose, two doses of 750 mg 2 h apart, and 750 mg every 6 h) indicated that in approximately 20% of patients the concentrations would still be below 0.5 mg/liter. Although oral ciprofloxacin may be a beneficial adjunctive therapy, the use of oral ciprofloxacin alone may not be adequate for perioperative prophylaxis or for treatment of bacterial endophthalmitis.

* Corresponding author. Mailing address: 592 Stirling Highway, Mosman Park, WA, 6012, Australia. Phone: 64 8 9385 6665. Fax: 64 8 9385 6669. E-mail: n-morlet{at}q-net.net.au.

Antimicrobial Agents and Chemotherapy, June 2000, p. 1674-1679, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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