Analysis of the electrophysiologic effects of short-term oxybutynin on guinea pig and rabbit ventricular cells

The objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding d ysfunction. Membrane currents were recorded from whole-cell-configured guin ea pig ventricular myocytes, and action potentials were recorded from guine a pig and rabbit papillary muscles. L-type Ca2+ current (I-Ca,I-L), inward- rectifier K+ current (I-K1), and delayed-rectifier K+ current (I-,I-\K) wer e unaffected by less than or equal to 1 mu M oxybutynin, and inhibited by h igher concentrations. The concentrations that reduced the currents to one-h alf of predrug control amplitude (K-0.5) were as follows: I-Ca,I-L, 16.1 mu M, I-K1, 18.2 mu M, rapidly activating I-K (I-Kr), 11.4 mu M, and slowly a ctivating I-K (I-s), 28.7 mu M Action-potential durations at 20 and 90% rep olarization (APD(20), APD(90)) were unaffected by oxybutynin less than or e qual to 3 mu M in guinea pig papillary muscles driven at 1 Hz; higher conce ntrations selectively shortened the APD(20) by as much as 25% (100 mu M), a nd caused moderate reductions in maximal upstroke velocity. Changes in the action potentials of rabbit papillary muscles were even smaller than in the guinea Dig muscles. Because the peak therapeutic plasma concentration of o xybutynin is in the 0.01-0.1 mu M range, the results suggest that the drug is highly unlikely to have adverse effects on cardiac electrical activity.