Enhancement of Nifedipine-Induced Gingival Overgrowth by Concomitant Ketoconazole in Rats

Nifedipine (NIF), a calcium channel blocker, is well known to induce gingival overgrowth (GO) as an adverse effect, and ketoconazole (KTZ), an azole antifungal agent, has been implicated in various drug interactions. We here examined the effects of concomitant KTZ on NIF-induced GO in a rat model. Fifteen-day-old male Fischer rats were fed chow with NIF, KTZ, or both. After 41 days, gingival conditions were evaluated and the concentration of NIF in serum was measured. Rats fed with NIF alone had induced GO and suppressed growth, while those given KTZ alone did not. Compared to the administration of NIF alone, concomitant KTZ significantly increased the severity of GO and the concentration of NIF in serum. These results suggest that concomitant KTZ increases the serum concentration of NIF and enhances the severity of GO.