Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{5d9a22df659843738c6d47e0ecbfaab9,
title = "The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis",
abstract = "We aimed to investigate the pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration of the combination of fosfomycin and metronidazole in patients undergoing laparoscopic appendectomy for uncomplicated appendicitis. We included eight otherwise healthy men undergoing laparoscopic appendectomy. The trial treatment was administered at the end of the surgical procedure and left in the abdominal cavity. Trial drugs consisted of 4 g fosfomycin and 1 g metronidazole in a total volume of 500.2 mL. Blood samples were collected prior to and ½, 1, 2, 4, 8, 12 and 24 h after administration. High-performance liquid chromatography-mass spectrometry was used for the measurement of plasma concentrations, and pharmacokinetic calculations were undertaken. Antimicrobial susceptibility testing was undertaken on isolates from intraoperatively collected specimens. The median maximal concentration for fosfomycin in plasma was 104.4 mg/L, median time point for the maximal concentration was 1.5 h, median half-life 3.0 h, and median area under the curve 608 mg*h/L. The median maximal concentration for metronidazole in plasma was 13.6 mg/L, median time point for the maximal concentration was 2.0 h, median half-life 7.3 h, and median area under the curve was 164 mg*h/L. All aerobic bacteria were susceptible to fosfomycin, and all anaerobes were susceptible to metronidazole. Plasma concentrations of fosfomycin and metronidazole were in line with concentrations reported from pharmacokinetic studies after intravenous administration and were within therapeutic ranges.",
keywords = "clinical trials, HPLC, pharmacokinetics, surgery",
author = "Siv Fonnes and Weisser, {Johan Juhl} and Holzknecht, {Barbara Juliane} and Magnus Arpi and Jacob Rosenberg",
note = "{\textcopyright} 2020 Soci{\'e}t{\'e} Fran{\c c}aise de Pharmacologie et de Th{\'e}rapeutique.",
year = "2020",
month = aug,
doi = "10.1111/fcp.12535",
language = "English",
volume = "34",
pages = "504--512",
journal = "Fundamental and Clinical Pharmacology",
issn = "0767-3981",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis

AU - Fonnes, Siv

AU - Weisser, Johan Juhl

AU - Holzknecht, Barbara Juliane

AU - Arpi, Magnus

AU - Rosenberg, Jacob

N1 - © 2020 Société Française de Pharmacologie et de Thérapeutique.

PY - 2020/8

Y1 - 2020/8

N2 - We aimed to investigate the pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration of the combination of fosfomycin and metronidazole in patients undergoing laparoscopic appendectomy for uncomplicated appendicitis. We included eight otherwise healthy men undergoing laparoscopic appendectomy. The trial treatment was administered at the end of the surgical procedure and left in the abdominal cavity. Trial drugs consisted of 4 g fosfomycin and 1 g metronidazole in a total volume of 500.2 mL. Blood samples were collected prior to and ½, 1, 2, 4, 8, 12 and 24 h after administration. High-performance liquid chromatography-mass spectrometry was used for the measurement of plasma concentrations, and pharmacokinetic calculations were undertaken. Antimicrobial susceptibility testing was undertaken on isolates from intraoperatively collected specimens. The median maximal concentration for fosfomycin in plasma was 104.4 mg/L, median time point for the maximal concentration was 1.5 h, median half-life 3.0 h, and median area under the curve 608 mg*h/L. The median maximal concentration for metronidazole in plasma was 13.6 mg/L, median time point for the maximal concentration was 2.0 h, median half-life 7.3 h, and median area under the curve was 164 mg*h/L. All aerobic bacteria were susceptible to fosfomycin, and all anaerobes were susceptible to metronidazole. Plasma concentrations of fosfomycin and metronidazole were in line with concentrations reported from pharmacokinetic studies after intravenous administration and were within therapeutic ranges.

AB - We aimed to investigate the pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration of the combination of fosfomycin and metronidazole in patients undergoing laparoscopic appendectomy for uncomplicated appendicitis. We included eight otherwise healthy men undergoing laparoscopic appendectomy. The trial treatment was administered at the end of the surgical procedure and left in the abdominal cavity. Trial drugs consisted of 4 g fosfomycin and 1 g metronidazole in a total volume of 500.2 mL. Blood samples were collected prior to and ½, 1, 2, 4, 8, 12 and 24 h after administration. High-performance liquid chromatography-mass spectrometry was used for the measurement of plasma concentrations, and pharmacokinetic calculations were undertaken. Antimicrobial susceptibility testing was undertaken on isolates from intraoperatively collected specimens. The median maximal concentration for fosfomycin in plasma was 104.4 mg/L, median time point for the maximal concentration was 1.5 h, median half-life 3.0 h, and median area under the curve 608 mg*h/L. The median maximal concentration for metronidazole in plasma was 13.6 mg/L, median time point for the maximal concentration was 2.0 h, median half-life 7.3 h, and median area under the curve was 164 mg*h/L. All aerobic bacteria were susceptible to fosfomycin, and all anaerobes were susceptible to metronidazole. Plasma concentrations of fosfomycin and metronidazole were in line with concentrations reported from pharmacokinetic studies after intravenous administration and were within therapeutic ranges.

KW - clinical trials

KW - HPLC

KW - pharmacokinetics

KW - surgery

UR - http://www.scopus.com/inward/record.url?scp=85078805279&partnerID=8YFLogxK

U2 - 10.1111/fcp.12535

DO - 10.1111/fcp.12535

M3 - Journal article

C2 - 31944378

VL - 34

SP - 504

EP - 512

JO - Fundamental and Clinical Pharmacology

JF - Fundamental and Clinical Pharmacology

SN - 0767-3981

IS - 4

ER -

ID: 60988118