Aim: To study the stereoselectivity of phase II glucuronidation metabolism of side-chain propranolol in Chinese Han population.
Methods: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC.
Results: The mean values of k were 0.19+/-0.04 h(-1) and 0.28+/-0.06 h(-1), of t(1/2) 3.56+/-0.73 h and 2.45+/-0.50 h, of T(max) 2.21+/-0.45 and 1.75+/-0.33 h, and of Xu(0-24) 5.65+/-0.98 and 2.95+/-0.62 micromoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of doses were 14.7+/-2.46% and 7.68+/-1.60% for S-(-)- and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t(1/2)), T(max) and the cumulative excretion amount(Xu(0-24)) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide.
Conclusion: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.