%0 Journal Article %1 Thiercelin1984 %A Thiercelin, J. F. %A Diquet, B. %A Levesque, C. %A Ghesquiére, F. %A Simon, P. %A Viars, P. %D 1984 %J Clin Pharmacol Ther %K metronidazole drug mucosal %N 4 %P 510--519 %R doi:10.1038/clpt.1984.69 %T Metronidazole kinetics and bioavailability in patients undergoing gastrointestinal surgery. %U http://dx.doi.org/10.1038/clpt.1984.69 %V 35 %X Kinetics and bioavailability of metronidazole were studied in 17 patients admitted in our emergency care unit for gastrointestinal surgery. All were treated with intravenous metronidazole (500 mg three times a day) before, during, and for 4 days after surgery. Seven of the patients continued the intravenous regimen and seven were switched to oral therapy with the same dose and dosing interval for 4 additional days. Kinetic evaluations were performed at steady state on days 4 and 8. The main unexpected result was a consistent 51\% increase in AUC with no increase in elimination t 1/2 when intravenous was changed to oral therapy. This change was accompanied by an upward 75\% shift in the trough metronidazole plasma concentrations. There was no change when patients remained on intravenous metronidazole. Reduction of clearance on oral treatment appears to be the most likely explanation.

@article{Thiercelin1984, abstract = {Kinetics and bioavailability of metronidazole were studied in 17 patients admitted in our emergency care unit for gastrointestinal surgery. All were treated with intravenous metronidazole (500 mg three times a day) before, during, and for 4 days after surgery. Seven of the patients continued the intravenous regimen and seven were switched to oral therapy with the same dose and dosing interval for 4 additional days. Kinetic evaluations were performed at steady state on days 4 and 8. The main unexpected result was a consistent 51\% increase in AUC with no increase in elimination t 1/2 when intravenous was changed to oral therapy. This change was accompanied by an upward 75\% shift in the trough metronidazole plasma concentrations. There was no change when patients remained on intravenous metronidazole. Reduction of clearance on oral treatment appears to be the most likely explanation.}, added-at = {2012-06-15T21:56:57.000+0200}, author = {Thiercelin, J. F. and Diquet, B. and Levesque, C. and Ghesquiére, F. and Simon, P. and Viars, P.}, biburl = {https://www.bibsonomy.org/bibtex/2c7a7ee06857909d8604cb72c17f78177/aorchid}, description = {51% higher AUC with oral metronidazole versus IV. Felt due to reduced clearance of oral metronidazole. Possible reasons include glucuronidation during oral therapy and subsequent release into the cirulation after de-glucuronidation. Another idea was that distribution includes gut flora and oral metronidazole kills off the flora due to higher intraluminal concentrations, thus reducing the volume of distribution. Suggest that if oral metronidazole is killing intraluminal bacteria, then the dose should be reduced. Either route the level in the blood (and therefore bile per another study) was always at least 6mg/l, higher than most MIC.}, doi = {doi:10.1038/clpt.1984.69}, file = {oral metronidazole higher AUC than IV:ID_General/ClinPharmacolTher.35.510.pdf:PDF}, groups = {public}, interhash = {994a12711469e31abfcffd1e1641106a}, intrahash = {c7a7ee06857909d8604cb72c17f78177}, journal = {Clin Pharmacol Ther}, keywords = {metronidazole drug mucosal}, language = {eng}, medline-pst = {ppublish}, month = Apr, number = 4, pages = {510--519}, pii = {0009-9236(84)90037-7}, pmid = {6705449}, timestamp = {2012-06-15T21:56:57.000+0200}, title = {Metronidazole kinetics and bioavailability in patients undergoing gastrointestinal surgery.}, url = {http://dx.doi.org/10.1038/clpt.1984.69}, username = {aorchid}, volume = 35, year = 1984 }