Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine after epidural administration

Abstract

Background. Pharmacokinetic and/or pharmacodynamic changes, which may occur with increasing age, could alter the clinical profile of the new local anaesthetic levobupivacaine. We investigated the effect of age on the absorption and disposition kinetics and the neural block characteristics after epidural administration of levobupivacaine 0.75%. Methods. Thirty-one patients were enrolled in one of three age groups (Group 1, 18-44 yr; Group 2, 45-70 yr; Group 3, >70 yr). Twenty-five minutes after epidural administration of levobupivacaine (127.5 mg), they received ∼25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected until 24 h after the epidural administration. Plasma concentrations were determined using liquid chromatography mass spectrometry. Plasma concentration-time data were analyzed by compartmental and noncompartmental analysis. Assessments of analgesia and motor block were made at set intervals until complete regression of the block. Results. The upper levels of analgesia in the two oldest groups of patients were 3 dermatomes (95% confidence interval (95% CI): 0.5-5.0 dermatomes) higher than in the youngest group. The fraction absorbed (F1) was 0.07 (95% CI: 0.02-013) smaller and the absorption half-life (t1/2,a1), characterizing the initial fast absorption phase, 3.6 min (95% CI: 0.8-6.4) shorter in the oldest group compared with the youngest group. Conclusions. Age influences the pharmacokinetics, in particular the early absorption kinetics, and the neural block characteristics after epidural administration of levobupivacaine. Changes in the upper level of analgesia are best explained by anatomical considerations and possibly pharmacodynamic changes in the elderly. © The Board of Management and Trustees of the British Journal of Anaesthesia 2004.