The Pharmacokinetics and Effects of Diltiazem in Rabbits

Purpose To investigate the effect of diltiazem on wound healing after the creation of conjunctival flaps in rabbit eyes. Also, to investigate the pharmacokinetics of diltiazem in rabbits after subconjunctival and topical administration.Methods For the histopathological study, a limbal-based flap was prepared and diltiazem was injected subconjunctivally for five days after the surgery. The rabbits were euthanised 20 days after surgery. The effectiveness of diltiazem on wound healing was evaluated by histopathological examination and measurement of the thickness of subconjunctival fibrous tissue. For the pharmacokinetic study, diltiazem was applied topically or injected subconjunctivally. Aqueous paracenteses were performed 0.5, 1, 2, 4 hours thereafter.Results The histopathological study found no difference in thickness of the subconjunctival fibrous tissue in control and diltiazem-treated eyes. No significant toxicity was observed in eyes treated with diltiazem. The peak aqueous concentration was 3.8 ± 0.4 μg/ml after topical application and 15.3 ± 1.1 μg/ml after subconjunctival injection. The peak aqueous concentration was achieved 1/2 hours after administration in both cases.Conclusions Diltiazem did not appear to affect wound healing at the dose tested. Topical and subconjunctival diltiazem successfully penetrated the aqueous humor of rabbit eyes.