REPOLARISATION ASSAYS

SINGLE VENTRICULAR MYOCYTES

EFFECTS OF SPARFLOXACIN ON ACTION POTENTIAL DURATION

 

Figure 1 The effect of sparfloxacin on action potential duration.

Figure 1 shows action potential records taken from a single left ventricular myocyte under our standard experimental conditions used for the action potential measurements in the absence (black) and presence (red) of sparfloxacin (100 鮼br> Sparfloxacin (1, 10 and 100 頍 caused concentration-dependent increase in action potential duration.  Prolongation of APD90 at 1 Hz was 7.3 ᮵% at 1 젍 18.5 㮴% at 10 젡nd 26.0 㮴% at 100 ͊ sparfloxacin.  Sparfloxacin elicited a similar prolongation of APD50.

 

 

Figure 2   Mean data for the effect of sparfloxacin on APD50 and APD90.

 
 

Figure 2 Sparfloxacin showed similar prolongations of APD50 and APD90 to those observed with the comparator compounds, dofetilide and sotalol.  Indeed the maximum prolongation of APD90 of 26.0 䮱% is consistent with that expected for complete block of IKr.  The effects of sparfloxacin on action potential duration recorded in guinea-pig ventricular myocytes are consistent with those previously reported in dog Purkinje fibres (Patmore et al, 2000) and with inhibition of HERG (the cloned IKr channel) by this compound (Bishoff et al.,2000; and Kang et al, 2000).

 

 
 

References

Patmore, L., Fraser, S., Mair, D., Templeton, A (2000) Effects of sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin on cardiac action potential duration. European J. of Pharm. 406 :499-452.

Kang, J., Wang, L., Chen, X., Triggle, D. and Rampe D. (2001) Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG. Mol Pharmacol 59:122-126.

Bischoff, U., Schmidt, C., Netzer, R. and Pongs, O. (2000) Effects of fluoroquinolones on HERG currents. European J of Pharm.406: 341-343.

 
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