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Metronidazole Impairs Clearance of Phenytoin but Not of Alprazolam or Lorazepam
Author(s) -
Blyden Gershwin T.,
Scavone Joseph M.,
Greenblatt David J.
Publication year - 1988
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1988.tb03139.x
Subject(s) - alprazolam , lorazepam , metronidazole , phenytoin , glucuronidation , pharmacology , glucuronide , hydroxylation , anticonvulsant , chemistry , metabolite , anesthesia , medicine , epilepsy , antibiotics , biochemistry , in vitro , anxiety , psychiatry , enzyme , microsome
Healthy volunteers received single doses of either phenytoin (300 mg IV), alprazolam (1 mg orally) or lorazepam (2 mg IV) on two occasions in random sequence. One of the two trials was a control; for the other trial, subjects ingested metronidazole, 250 mg three times daily beginning 4 days prior to and continuing for the duration of each kinetic study. Compared with control, metronidazole significantly prolonged phenytoin half‐life (23 versus 16 hours, P < .02) and reduced its clearance (.28 versus .33 mL/min/kg, P < .005), known to depend on aromatic hydroxylation. However, metronidazole did not significantly alter kinetic variables for either alprazolam (metabolized by aliphatic hydroxylation) or lorazepam (metabolized by glucuronide conjugation). Thus, metronidazole has the capacity to impair the clearance of certain oxidatively metabolized drugs, but there is no apparent way to predict which drugs will be so influenced.