Effects of nadolol and propranolol on plasma lidocaine clearance

Nadolol and propranolol effects on lidocaine elimination were followed in six healthy men and women. Each received three separate 30‐hr infusions of lidocaine (2 mg/min): one alone, one after 3 days pretreatment with nadolol (160 mg daily), and one after 3 days pretreatment with propranolol (80 mg every 8 hr). Liver blood flow was determined by the systemic clearance of indocyanine green. Steady‐state plasma lidocaine levels were increased by nadolol (2.1 ± 0.2 to 2.7 ± 0.3 μg/ml) and by propranolol (2.1 ± 0.2 to 2.5 ± 0.3 μg/ml). Lidocaine plasma clearance was decreased by nadolol (1030 ± 81 to 850 ± 82 ml/min) and by propranolol (1030 ± 81 to 866 ± 75 ml/min). Hepatic blood flow was decreased by nadolol (1275 ± 77 to 902 ± 102 ml/min) and propranolol (1275 ± 77 to 957 ± 119 ml/min). The hepatic extraction ratio for lidocaine was increased by nadolol (0.86 ± 0.06 to 0.91 ± 0.05) and by propranolol (0.86 ± 0.06 to 0.90 ± 0.06). Lidocaine intrinsic clearance was not changed by nadolol (8.19 ± 1.87 to 9.52 ± 2.36 l/min) or propranolol (8.19 ± 1.87 to 9.50 ± 3.13 l/min). Our data indicate that both nadolol and propranolol reduce lidocaine clearance by their effects on hepatic blood flow and not by inhibition of lidocaine metabolism. Clinical Pharmacology and Therapeutics (1984) 36, 584–587; doi: 10.1038/clpt.1984.225