Effect of cardiopulmonary bypass on the pharmacokinetics of intravenous paracetamol [Propacetmol hydrochloride]

ABSTRACT

Recently, intravenous paracetamol [propacetamol] is commonly in use as analgesic and antipyretic after surgery. To our knowledge, the pharmacokinetic of intravenous paracetamol in patients undergoing cardiac surgery with cardiopulmonary bypass were not previously described. This study was designed to investigate the effect of cardiopulmonary bypass on the pharmacokinetics of single intravenous dose of paracetamol in adult patients undergoing coronary artery bypass surgery with hypothermic cardiopulmonary bypass. Nine patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass using mild hypothermia 30°C were selected. Intravenous paracetamol [2g single dose of Propacetamol hydrochloride [Pro-Daflgan UPSA, Fr]] was infused over 10 min and arterial samples were taken starting from 20 min after infusion and afterwards over 8 hours from infusion. Plasma paracetamol concentrations were measured by high-pressure liquid chromatography. The pharmacokinetics of paracetamol was calculated assuming a linear one compartment model with instantaneous input and first order output. The pharmacokinetic data were reported as mean [SD]. ANOVA was used to compare between the pharmacokinetic parameters before and after CPB. C[max] 10.19 [0.9545] mg.litre[-1] appeared 20 min after the end of infusion [experimentally]. Mean clearance [CL] was significantly reduced by about 40% in post CPB [prebypass 0.589 [0.1069] L.h[-1].kg[-1] vs. 0.357 [0.0394] L.h[-1].kg[-1] after CPB, P < 0.05]. The elimination rate constant [Ke] was significantly reduced by about 43% after CPB compared to pre-bypass values. However, the elimination half-life [t[1/2]] was significantly increased from 1.380 h before bypass to 2.431h in post bypass period. It appears from this study that hypotuermic cardiopulmonary bypass can affect the kinetic profile of IV paracetamol in patients undergoing coronary artery bypass graft surgery, and these changes should be considered while using this drug in such situations