Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial agent in intravenous use. I. Effects of doses and infusion rate on blood pressure, heart rate and plasma histamine concentration.
T-3762, a newly developed fluoroquinolone antimicrobial agent, ciprofloxacin (CPFX) and ofloxacin (OFLX) were administered intravenously to anesthetized dogs by intravenous infusion, and blood pressure, heart rate and plasma histamine concentrations were monitored. T-3762 decreased blood pressure by 12.0%, without alterations in heart rate and plasma histamine concentration, only when infused at 150 mg/min. CPFX and OFLX both produced a rapid decrease in blood pressure in a dose-related manner, with an accompanying decrease in heart rate, but to a lesser extent. After infusion at 150 mg/min, CPFX caused death in 2 animals within a few minutes, while OFLX produced maximum decreases in blood pressure and heart rate, by 69.0% and 26.4%, respectively. The infusion of these 2 agents resulted in dose-related increases in plasma histamine concentrations parallel to the decreases in blood pressure: the maximum, attained with CPFX at 50 mg/min and OFLX at 150 mg/min, were 379.2 and 167.8 ng/ml, respectively. For CPFX and OFLX, the relationship between the maximum levels of decreased blood pressure and increased histamine concentration in plasma was highly significant. The hypotension induced by CPFX was efficiently reduced by the pretreatment of animals with antihistamines. The results from this study suggest that hypotension induced in dogs following the intravenous infusion of fluoroquinolone antimicrobial agents may be dependent on their ability to cause histamine release from cells and tissues, and indicates that T-3762 is devoid of this ability in comparison to CPFX and OFLX.
Furuhata
K
K
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Hayakawa
H
H
Soumi
K
K
Arai
H
H
Watanabe
Y
Y
Narita
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002939:Ciprofloxacin / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000097:blood; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D015242:Ofloxacin / Q000494:pharmacology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D006633:Histamine Antagonists; C113785:T 3762; D002939:Ciprofloxacin; D006632:Histamine; D015242:Ofloxacin