Effects of nadolol and propranolol on plasma lidocaine clearance

Abstract

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 micrograms/ml) and by propranolol (2.1 +/- 0.2 to 2.5 +/- 0.3 micrograms/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.