Interaction of tertatolol with rifampicin and ranitidine pharmacokinetics and antihypertensive activity

Summary

The interaction of the new beta-receptor antagonist tertatolol with rifampicin and ranitidine was investigated in ten patients with arterial hypertension (WHO stages I–II). They were treated orally with a single dose of tertatolol 5 mg alone and, after randomized allocation, with ranitidine 150 mg twice daily or rifampicin 600 mg once daily for 1 week each (tertatolol 5 mg was concurrently administered on the seventh day of the treatment phases). Following each therapeutic phase, circadian blood pressure values as well as kinetic parameters were obtained. On treatment with tertatolol alone, maximum plasma concentrations were 123.7 ±32.4 ng/ml$(\bar X \pm SD)$ and were reached after 1.95±1.77 hours. The tertatolol elimination half-life was 9.0±7.1 hours. Coadministration of ranitidine did not significantly alter the kinetic parameters and antihypertensive effect of tertatolol. Rifampicin, however, decreased the maximum plasma levels of tertatolol to 80.6±18.5 ng/ml and markedly shortened the elimination half-life to 3.4±2.6 hours (p<0.01 compared with tertatolol alone). Urinary excretion of parent tertatolol and unchanged 4-hydroxy tertatolol was decreased under rifampicin, and a tendency to a reduction in the effect of tertatolol on circadian blood pressure values was observed. Twenty-four hours after administration, the heart rate in those patients on tertatolol alone (68±6 beats/min) was lower than in those on tertatolol plus rifampicin (74±7 beats/min). In conclusion, a pronounced pharmacokinetic interaction, with a limited consequence in terms of pharmacodynamic effects, was found in the present study when tertatolol was administered with rifampicin, but not with ranitidine.