Multiple dose pharmacokinetics and relative bioavailability of ambroxol hydrochloride sustained release capsules in healthy volunteers

AIM To study the multiple dose pharmacokinetics and relative bioavailability of ambroxol hydrochloride sustained release capsules in 12 male healthy volunteers. METHODS A reversed phase high performance liquid chromatography (RP HPLC) with quinine dihydrochloride as the internal standard was established for the determination of ambroxol hydrochloride in plasma after multiple administration of a daily dose of 75 mg ambroxol hydrochloride domestic and imported sustained release capsules in a randomized crossover design.The fluctuation of ambroxol hydrochloride valley concentrations was observed and the steady state pharmacokinetics was characterized in a multiple dose schedule of 75 mg ambroxol hydrochloride sustained release capsules. RESULTS The steady state of ambroxol hydrochloride plasma concentrations was reached at the fourth oral administration of 75 mg ambroxol hydrochloride sustained release capsules. The steady state pharmacokinetic parameters after multiple oral dose of 75 mg ambroxol hydrochloride domestic and imported sustained release capsules were as follows: T max were (4 2±0 7) h and (4 1±0 8) h, C max were (208 73±31 91)μg·L -1 and (212 56±29 64) μg·L -1 , C min were (30 76±10 47)μg·L -1 and (29 80±10 23)μg·L -1 , AUC ss were (2113 90±430 60)μg·h -1 ·L -1 and 2088 22±402 52 μg·h·L -1 , C av were (88 08±17 94)μg·L -1 and (87 01±16 77)μg·L -1 , DF were (2 07±0 31) and (2 16±0 37), respectively. The relative bioavailability of multiple oral dose of 75 mg domestic ambroxol hydrochloride sustained release capsules was 101 10%±6 33%. CONCLUSION There were no significant differences in the main steady state pharmacokinetic parameters between domestic, and imported sustained release capsules and the two capsules were bioequivalent.