Relationship between plasma concentration of β-hydroxybutyrate, acetoacetate, lactate and pyruvate and alcohol after oral or intravenous administration of alcohol to normal human subjects: a population pharmacodynamics (PD) analysis
WAN Jie, LI Jian-guo, HUI C ko, Tom LIONETTI, David T GEORGE, Susan E SHOAF
2005, 10(1):
29-39.
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AIM: To investigate the relationship between plasma concentration of β-hydroxybutyrate, acetoacetate, lactate, pyruvate, β-hydroxybutyrate acetoacetate (H/A ratio) and lactate/pyruvate (L/P ratio) and alcohol by population PD analysis after oral or intravenous administration of alcohol.METHODS: An oral dose of alcohol equivalent to 1.02 g·L-1total body water was administered to 14 normal human subjects and an IV infusion (30 min) dose of alcohol equivalent to 0.83 g·L-1total body water was administered to 8 normal subjects.Venous blood was sampled for determination of alcohol (BAC), β-hydroxybutyrate, acetoacetate, lactate and pyruvate for 380 min after oral administration and for 340 min after IV administration.RESULTS: After oral administration, the average of C0 for BAC was 666±81 mg·L-1, and it was significantly lower than 1 020 mg·L-1(P <0.001). The slope β for eliminate-phase was 2.29±0.50 mg·L-1·min-1.After IV administration, C0 was 756±109 mg·L-1, and the slope β for eliminate-phase was 2.45±0.51 mg·L-1·min-1.The C0 was not significantly different from the expected value of 830 mg·L-1.After oral or IV administration, the relationship between BAC and β-hydroxybutyrate, acetoacetate, lactate and pyruvate concentration and H/A and L/P ratio were investigated by population physiologic indirect response model, and the parameters were presented.Meanwhile, the H A did not reach maximum at the end of the elimination phase of the alcohol, and it suggested that the liver continue to accumulate NADH at zero-orden metabolism phase of alcohol. The plot of BAC versus the plasma concentration of lactate showed an apparent counter-clockwise hysteresis.CONCLUSION: In general, venous blood L P ratio is not a suitable index for the real time reflection of liver redox status because of the time lag change in concentration of lactate after administration of ethanol.The parameters provided here can be useful for future researches on the effect of alcohol on liver redox status.
