The Effect of Age on the Systemic Absorption, Disposition and Pharmacodynamics of Bupivacaine After Epidural Administration
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The influence of age on the systemic absorption and disposition of bupivacaine following epidural administration in 20 male patients (22 to 81 years) was examined using a stable isotope method to determine whether pharmacokinetics play a role in age-related pharmacodynamic changes seen with the drug. After epidural bupivacaine administration a deuterium-labelled analogue was administered intravenously. Bi- and triexponential functions were fitted to plasma concentration-time data of deuterium-labelled bupivacaine. The systemic absorption was described by 2 parallel first-order absorption processes. The upper level of analgesia and the duration of analgesia at dermatome T-12 increased with age (r = 0.68, p < 0.001; r = 0.56, p < 0.01, respectively). The time to maximal caudad spread of analgesia and the time to onset of motor block decreased with age (r = −0.76, p < 0.0001; r = −0.72, p < 0.001, respectively). Age did not influence systemic absorption or disposition of bupivacaine. We conclude that the changes in the clinical profile of bupivacaine with age are not due to altered pharmacokinetics, but may be related to changes in the pharmacodynamics of the drug.
KeywordsBupivacaine Epidural Space Systemic Absorption Mean Residence Time Motor Block
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