The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis
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The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis. / Fonnes, Siv; Weisser, Johan Juhl; Holzknecht, Barbara Juliane; Arpi, Magnus; Rosenberg, Jacob.
In: Fundamental and Clinical Pharmacology, Vol. 34, No. 4, 2020, p. 504-512.Research output: Contribution to journal › Journal article › Research › peer-review
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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
PY - 2020
Y1 - 2020
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
U2 - 10.1111/fcp.12535
DO - 10.1111/fcp.12535
M3 - Journal article
C2 - 31944378
AN - SCOPUS:85078805279
VL - 34
SP - 504
EP - 512
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
SN - 0767-3981
IS - 4
ER -
ID: 258447454