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Enhancement of nifedipine-induced gingival overgrowth by concomitant ketoconazole in rats
Takahiro Kato1, Atsuo Amano, Yoshinori Kamisaki
1Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Abstract:
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.
Insights
Concomitant use of ketoconazole (KTZ) with nifedipine (NIF) significantly worsens nifedipine-induced gingival overgrowth (GO) in rats. KTZ increases NIF serum levels, exacerbating this common adverse drug effect.
Area of Science:
- Pharmacology
- Drug Interactions
- Oral Medicine
Background:
- Nifedipine (NIF), a calcium channel blocker, is a known cause of gingival overgrowth (GO).
- Ketoconazole (KTZ), an azole antifungal, is associated with various drug interactions.
- The combined effect of NIF and KTZ on GO is not well understood.
Purpose of the Study:
- To investigate the impact of concomitant ketoconazole (KTZ) administration on nifedipine (NIF)-induced gingival overgrowth (GO) in a rat model.
Main Methods:
- Male Fischer rats were administered NIF, KTZ, or both concurrently via chow for 41 days.
- Gingival overgrowth severity and serum NIF concentrations were evaluated post-treatment.
Main Results:
- Nifedipine administration alone induced gingival overgrowth and suppressed growth.
- Ketoconazole administration alone did not cause gingival overgrowth.
- Concomitant KTZ administration significantly increased the severity of NIF-induced GO and elevated serum NIF concentrations compared to NIF alone.
Conclusions:
- Ketoconazole exacerbates nifedipine-induced gingival overgrowth.
- Increased serum nifedipine concentration is a likely mechanism for the enhanced GO severity.
- This interaction highlights potential risks for patients on both medications.
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