Also poorly metabolized drugs, including certain beta-blocking agents, can be susceptible to drug interactions caused by transporter inhibitors and inducers. Thus, our aim was to investigate the effect of rifampicin on the pharmacokinetics of atenolol in healthy people. In a randomized cross-over study with two phases, nine healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 100 mg dose of atenolol was administered orally. The plasma concentrations of atenolol and its excretion into urine were measured up to 33 hr after dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the intake of atenolol and 2, 4, 6, and 10 hr later. During the rifampicin phase, the mean area under the plasma concentration-time curve (AUC(0-infinity)) of atenolol was decreased to 81% and renal clearance increased to 109% of the placebo phase values (P<0.05). Rifampicin pretreatment reduced, albeit not statistically significantly, also the peak plasma concentration (Cmax), AUC(0-33 hr), and amount of atenolol excreted to 85% (P=0.139), 81% (P=0.053), and 86% (P=0.12) of the respective placebo phase values. The average heart rate and diastolic blood pressure were slightly higher during the rifampicin phase compared with the placebo phase (P<0.05). To conclude, although the inducing effect of rifampicin may not have been at its maximum by day 6, rifampicin has only a minor effect on the pharmacokinetics of atenolol evidenced by a slight reduction in its bioavailability.