Enhancement of nadolol elimination by activated charcoal and antibiotics

This study was carried out to assess whether nadolol undergoes enterohepatic circulation. Eight healthy subjects received 80 mg nadolol orally on three occasions at least 2 wk apart. The first experiment was a control. The second consisted of nadolol followed in 3 hr by 3 gm activated charcoal given over a 9-hr period. In the third, the subjects received 0.5 gm erythromycin base and 0.5 gm neomycin four times a day orally for 2 days before nadolol. After the activated charcoal, the nadolol AUC fell from 2455 +/- 155 to 1355 +/- 123 ng . hr/ml (mean +/- SE), as did the percentage nadolol recovered in urine (15.4 +/- 1.4 to 10.2 +/- 0.7%) and the nadolol t1/2 (17.3 +/- 1.7 to 11.8 +/- 1.6 hr). These data suggest that nonrenal elimination increased. After the antibiotics, nadolol AUC was constant, percentage of nadolol recovered in urine fell to 12.7 +/- 1.7%, nadolol t1/2 fell to 11.6 +/- 1.3 hr, and mean peak nadolol concentration rose from 146 +/- 15 to 397 +/- 52 ng/ml. These results suggest that there is an enterohepatic circulation for nadolol, that activated charcoal may decrease nadolol bioavailability, and that antibiotics may increase the nadolol effect.