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First-pass or pre-systemic drug metabolism, which contributes to inter-individual variability of serum levels after oral administration, is traditionally attributed to cytochrome P450 (CYP) isoenzymes in the liver. This innovative study of midazolam's metabolism by CYP3A4, done during liver transplantation, suggests that a significant amount of first-pass metabolism also occurs in the small intestine.
The authors studied midazolam's metabolism to its principal metabolite after it was administered either intravenously or directly into the duodenum during transplantation in 10 patients. Any midazolam metabolism during the anhepatic phase would represent CYP3A4 activity elsewhere than in the liver.
During the anhepatic phase of surgery, portal v…