Abstract
We studied the distribution of doripenem (DRPM), a new carbapenem antibiotic for injection, in ocular tissue (aqueous humor) after DRPM infusion at a dosage of 250mg, and evaluated the efficacy and safety of DRPM administered in patients with corneal ulcer, orbital infection, and endophthalmitis after DRPM infusion at a dosage of 250mg, b. i. d. or t. i. d., or at 500mg, b. i. d.
DRPM concentration in the aqueous humor of those undergoing cataract surgery was 0.16-0.87mg/mL within 70-115 minutes of the start of infusion. Plasma concentration in the same period was 6.86-12.9μg/mL.
Of 15 patients evaluated for efficacy-corneal ulcer in 10, orbital infection in 4, and endophthalmitis in 1-DRPM was administered to 9 at a dose of 250mg b. i. d., to 3 at a dose of 250mg t. i. d., and to 3 at a dose of 500mg b. i. d. Clinical efficacy, the primary endpoint in this study, was 100.0%(15/15). Improvement on Day 2, a secondary endpoint, was 100%(15/15).
Bacteriological response was evaluated in 8 patients-corneal ulcer in 4, orbital infection in 3 and endophthalmitis in 1-1 of whom had α-Streptococcus infection, 3 Corynebacterium sp. infection, 2 P. aeruginosa infection, 1 P. acnes infection, and 1 S. aureus-P. intermedia mixed infection. Causative bacteria were eradicated in all 8 and no new strains appeared after DRPM administration.
All 15 were evaluated for safety, with the primary endpoint the absence or presence of adverse drug reactions (symptoms and laboratory findings) and the secondary endpoint overall safety. In 4, the 8 adverse events observed were mild to moderate and none was judged to be related to DRPM. In the abnormal laboratory findings reported in 5 (5 events), the causal relationship to DRPM could not be ruled out resulting in these 5 adverse events judged to be adverse drug reactions (abnormal laboratory findings), including an increase in ALT (3 events), an increase in AST (1), and an increase in γ-GPT (1). The incidence of adverse drug reactions was 33.3%(5/15) and all were mild and returned to normal. Many of these adverse drug reactions (abnormal laboratory findings) were similar to those of currently available carbapenem antibiotics. The overall safety of DRPM was 100.0%(15/15).
