title: Prulifloxacin: in vitro (HERG current) and in vivo (conscious dog) assessment of cardiac risk.
abstract: Prulifloxacin, a new thiazeto-quinoline derivative with antibiotic properties, was evaluated for cardiac risk both in vitro on the ether-à-go-go-related gene (HERG) K+ channel, and in vivo in the conscious dog monitored by telemetry. HERG current was measured from stably transfected human embryonic kidney (HEK) 293 cells by means of the patch-clamp technique. Application of AF 3013, the active metabolite of prulifloxacin, produced only minor reduction of HERG current amplitude (tail current=-40 mV), producing a maximum blockade of 12.3 +/- 3.3% at the highest concentration tested (335 microM). In comparison, ciprofloxacin also failed to produce a 50% inhibition of HERG current amplitude, although the maximum blockade was greater than that observed with prulifloxacin (47.6 +/- 1.9% at the highest concentration tested (335 microM). In contrast, moxifloxacin blocked HERG current amplitude with an IC50 value of 74.7 microM. Prulifloxacin had no effect on the QTc interval (Fridericia's) following 5 days of repeated oral administration (150 mg/kg/day) in the conscious dog monitored by telemetry. These findings suggest that prulifloxacin is not likely to prolong the QT interval.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology; D001372:Aza Compounds / Q000009:adverse effects / Q000494:pharmacology; D002460:Cell Line; D002939:Ciprofloxacin / Q000009:adverse effects / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D004148:Dioxolanes / Q000009:adverse effects* / Q000494:pharmacology; D004285:Dogs; D024841:Fluoroquinolones / Q000009:adverse effects* / Q000494:pharmacology; D066298:In Vitro Techniques; D000077266:Moxifloxacin; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000009:adverse effects* / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000009:adverse effects* / Q000494:pharmacology; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology; D015363:Quinolones / Q000009:adverse effects* / Q000494:pharmacology; D013686:Telemetry; D015534:Trans-Activators / Q000187:drug effects* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D004268:DNA-Binding Proteins; D004148:Dioxolanes; C072312:ERG protein, human; D024841:Fluoroquinolones; D010879:Piperazines; D026902:Potassium Channel Blockers; D011804:Quinolines; D015363:Quinolones; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D002939:Ciprofloxacin; C074191:prulifloxacin; D000077266:Moxifloxacin