Elliot V Hersh1, Paul A Moore. 1. University of Pennsylvania School of Dental Medicine, Philadelphia 19104-6030, USA. evhersh@pobox.upenn.edu
Abstract
BACKGROUND: The hepatic and intestinal cytochrome, or CY, P450 enzyme system is responsible for the biotransformation of a multitude of drugs. Certain medications used in dentistry can act as substrates, inducers or inhibitors of this system. METHODS: The authors conducted a MEDLINE search of articles appearing between 1976 and the present using the keywords "drug interactions" and "cytochrome P450," and reviewed reports involving dental therapeutic agents using PubMed links from an Indiana University CYP450 drug interaction table on the World Wide Web. RESULTS: The antibiotics erythromycin and clarithromycin are potent inhibitors of CYP3A4 and can increase blood levels and toxicity of CYP3A4 substrates. Likewise, quinolone antibiotics such as ciprofloxacin inhibit the metabolism of CYP1A2 substrates. Other dental therapeutic agents are substrates for CYP2C9 (celecoxib, ibuprofen and naproxen), CYP2D6 (codeine and tramadol), CYP3A4 (methylprednisolone) and CYP2E1 (acetaminophen). Because codeine and tramadol are prodrugs, inhibition of their metabolism can lead to a diminution of their analgesic effects. While inducers of acetaminophen metabolism, including alcohol, theoretically can increase the proportion of it that is biotransformed into a potentially hepatotoxic metabolite, recent research suggests that concomitant alcohol intake does not increase the hepatotoxic potential of therapeutic doses of acetaminophen. CONCLUSIONS: A number of clinically significant drug interactions can arise with dental therapeutic agents that act as substrates or inhibitors of the CYP450 system. Clinical Implications. As polypharmacy continues to increase, the likelihood of adverse drug interactions in dentistry will increase as well. Ensuring that patients' medical histories are up to date and acquiring knowledge of the various substrates, inducers and inhibitors of the CYP450 system will help practitioners avoid potentially serious adverse drug interactions.
BACKGROUND: The hepatic and intestinal cytochrome, or CY, P450 enzyme system is responsible for the biotransformation of a multitude of drugs. Certain medications used in dentistry can act as substrates, inducers or inhibitors of this system. METHODS: The authors conducted a MEDLINE search of articles appearing between 1976 and the present using the keywords "drug interactions" and "cytochrome P450," and reviewed reports involving dental therapeutic agents using PubMed links from an Indiana University CYP450 drug interaction table on the World Wide Web. RESULTS: The antibiotics erythromycin and clarithromycin are potent inhibitors of CYP3A4 and can increase blood levels and toxicity of CYP3A4 substrates. Likewise, quinolone antibiotics such as ciprofloxacin inhibit the metabolism of CYP1A2 substrates. Other dental therapeutic agents are substrates for CYP2C9 (celecoxib, ibuprofen and naproxen), CYP2D6 (codeine and tramadol), CYP3A4 (methylprednisolone) and CYP2E1 (acetaminophen). Because codeine and tramadol are prodrugs, inhibition of their metabolism can lead to a diminution of their analgesic effects. While inducers of acetaminophen metabolism, including alcohol, theoretically can increase the proportion of it that is biotransformed into a potentially hepatotoxic metabolite, recent research suggests that concomitant alcohol intake does not increase the hepatotoxic potential of therapeutic doses of acetaminophen. CONCLUSIONS: A number of clinically significant drug interactions can arise with dental therapeutic agents that act as substrates or inhibitors of the CYP450 system. Clinical Implications. As polypharmacy continues to increase, the likelihood of adverse drug interactions in dentistry will increase as well. Ensuring that patients' medical histories are up to date and acquiring knowledge of the various substrates, inducers and inhibitors of the CYP450 system will help practitioners avoid potentially serious adverse drug interactions.
Authors: Michael L Booker; Cecilia M Bastos; Martin L Kramer; Robert H Barker; Renato Skerlj; Amar Bir Sidhu; Xiaoyi Deng; Cassandra Celatka; Joseph F Cortese; Jose E Guerrero Bravo; Keila N Crespo Llado; Adelfa E Serrano; Iñigo Angulo-Barturen; María Belén Jiménez-Díaz; Sara Viera; Helen Garuti; Sergio Wittlin; Petros Papastogiannidis; Jing-Wen Lin; Chris J Janse; Shahid M Khan; Manoj Duraisingh; Bradley Coleman; Elizabeth J Goldsmith; Margaret A Phillips; Benito Munoz; Dyann F Wirth; Jeffrey D Klinger; Roger Wiegand; Edmund Sybertz Journal: J Biol Chem Date: 2010-08-11 Impact factor: 5.157