A 45-year-old man suffering from epilepsy had been receiving carbamazepine, one tablet daily. The drug has a total clearance of 63 L/h and a hepatic clearance of 62 L/h. The man was recently diagnosed with a skin infection due to Mycobacterium marinum , and treatm ent wიth rifampin and ethambutol was started. Know ing that rifampin is a potent inducer of microsomal enzymes, which of the following changes most likely occurred to the pharmacokinetics of carbamazepine?
1

The hepatic clearance of the drugs decreased
2

The renal clearance of the drug decreased.
3

The half-life of the drug decreased
4

The first-pass loss of the drug decreased



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