TY - JOUR
T1 - Concentrations of trovafloxacin in colonic tissue and peritoneal fluid after intravenous infusion of the prodrug alatrofloxacin in patients undergoing colorectal surgery
AU - Melnik, George
AU - Schwesinger, Wayne H.
AU - Dogolo, Lisa C.
AU - Teng, Renli
AU - Vincent, John
N1 - Funding Information:
This work was supported by a grant from the Central Research Division, Pfizer Inc, Groton, Connecticut.
PY - 1998/12
Y1 - 1998/12
N2 - BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective colorectal surgery. Alatrofloxacin is a prodrug that is rapidly hydrolyzed to trovafloxacin in the body. METHODS: Twelve patients received a single dose of alatrofloxacin equivalent to 200 mg trovafloxacin by intravenous infusion over 1 hour. Surgery was started at various time points relative to infusion time to allow determination of trovafloxacin concentrations in serum, colonic tissue, and peritoneal fluid as a function of time. RESULTS: The concentration in the earliest colonic tissue sample (1.4 hours after dosing) was 1.4 μg/g. The maximum colonic tissue concentration was 2.8 μg/g in a sample taken 2 hours after dosing. Colonic tissue/serum concentration ratios in samples taken 2-10 hours after the end of infusion ranged from 0.8 to 1.47. Concentrations of trovafloxacin in peritoneal fluid ranged from below the level of quantitation to 2.1 μg/mL at the time of colonic tissue sampling and from below the level of quantitation to 2.5 μg/mL at the time of wound closure. Alatrofloxacin was well tolerated. CONCLUSIONS: After a single intravenous dose of alatrofloxacin equivalent to 200 mg trovafloxacin, trovafloxacin is distributed rapidly into colonic tissue and peritoneal fluids. Tissue concentrations approximate serum concentrations and decline in parallel for up to 10 hours after dosing.
AB - BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective colorectal surgery. Alatrofloxacin is a prodrug that is rapidly hydrolyzed to trovafloxacin in the body. METHODS: Twelve patients received a single dose of alatrofloxacin equivalent to 200 mg trovafloxacin by intravenous infusion over 1 hour. Surgery was started at various time points relative to infusion time to allow determination of trovafloxacin concentrations in serum, colonic tissue, and peritoneal fluid as a function of time. RESULTS: The concentration in the earliest colonic tissue sample (1.4 hours after dosing) was 1.4 μg/g. The maximum colonic tissue concentration was 2.8 μg/g in a sample taken 2 hours after dosing. Colonic tissue/serum concentration ratios in samples taken 2-10 hours after the end of infusion ranged from 0.8 to 1.47. Concentrations of trovafloxacin in peritoneal fluid ranged from below the level of quantitation to 2.1 μg/mL at the time of colonic tissue sampling and from below the level of quantitation to 2.5 μg/mL at the time of wound closure. Alatrofloxacin was well tolerated. CONCLUSIONS: After a single intravenous dose of alatrofloxacin equivalent to 200 mg trovafloxacin, trovafloxacin is distributed rapidly into colonic tissue and peritoneal fluids. Tissue concentrations approximate serum concentrations and decline in parallel for up to 10 hours after dosing.
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U2 - 10.1016/S0002-9610(98)00214-1
DO - 10.1016/S0002-9610(98)00214-1
M3 - Article
C2 - 9935251
AN - SCOPUS:0032466996
VL - 176
SP - 14S-17S
JO - American Journal of Surgery
JF - American Journal of Surgery
SN - 0002-9610
IS - 6 A
ER -