Biliary excretion and enterohepatic recirculation of practolol in man

Summary

The elimination of practolol in bile was studied in six patients who received a single oral dose of 400 mg within six days of undergoing biliary surgery. Bile collections were made from a T-tube drain left in the common bile duct after removal of multiple biliary calculi. There was wide variation in the concentration of practolol in bile and in the total amount of practolol excreted in bile during the 48 hour period after dosage. Two patients excreted 23 per cent and 41 per cent of the 400 mg dose in bile, whereas the excretion in the other four patients was only one per cent to four per cent of the oral dose. The mean urinary excretion of practolol in 48 hours was 74.2±S.E. 8.4 per cent of the ingested dose, and the total elimination (biliary plus urinary) was 86.5±S.E. 7.6 per cent. The total elimination ranged from 92 per cent to 105 per cent in four of the patients. The mean elimination half-life of practolol in blood was 6.4±S.E. 0.5 hours. This was significantly less than the half-life in normal subjects receiving the same practolol dose. Since complete or near-complete urinary excretion of practolol is found in normal subjects, the presence of large amounts of drug in the bile suggests that enterohepatic recirculation of the drug occurred in some of the patients at least. This is a possible explanation of the shortened half-life in these patients in whom drug was being removed with bile. The four patients with low excretion of practolol in bile were receiving other drugs at the time of the study. These included nitrazepam, diazepam and tetracycline which are known to have substantial biliary elimination either in animals or man. It is suggested that competition for biliary excretion may have occurred and this may represent a drug interaction of possible clinical significance.