Arterial and venous blood sampling in pharmacokinetic studies: bumetanide in rabbits

The pharmacokinetics of bumetanide were evaluated simultaneously using both arterial and venous plasma data in 4 rabbits after a rapid 5 sec intravenous (iv) bolus dosing. Initial arterial to venous concentration ratios at 5 sec after injection were the highest with the values of 1410, 246, 4.25, and 351 for rabbits 1-4, respectively. Both curves decayed paralleling each other at the terminal phase with the higher venous levels than the arterial levels by 21.6, 48.2, 17.0, and 47.9% for rabbits 1-4, respectively. An exponential term with a negative coefficient was used to account for the short and steep rising phase of venous plasma levels after injection. Detailed analysis showed apparent volume of distribution at steady state (VSS) and mean residence time (MRT) values calculated from venous plasma data were higher than those form arterial plasma data. A plot of 1/Q (urine flow rate) versus 1/CLR (renal clearance) of bumetanide yielded a straight line in 4 rabbits, indicating that the CLR of bumetanide is urine flow dependent in rabbits.