title: The effect of age on the systemic absorption and systemic disposition of ropivacaine after epidural administration.
abstract: Knowledge about the systemic absorption and disposition of ropivacaine after epidural administration is important in regard to its clinical profile and the risk of systemic toxicity. We investigated the influence of age on the pharmacokinetics of ropivacaine 1.0% after epidural administration, using a stable-isotope method. Twenty-four patients were enrolled in 1 of 3 groups according to age (group 1: 18-40 yr; group 2: 41-60 yr; group 3: > or =61 yr). Patients received 150 mg ropivacaine hydrochloride epidurally. After 25 min, patients received 50 mL 0.44 mg/mL deuterium-labeled ropivacaine (D3-ropivacaine) IV. Arterial blood samples were collected up to 24 h after epidural administration. Total plasma concentrations of ropivacaine and D3-ropivacaine were determined using liquid chromatography mass spectrometry. In the oldest patients, elimination half-life was significantly longer (ratio of the geometric means 0.60; 95% confidence interval, 0.37-0.99) and clearance was significantly decreased (mean difference, 194 mL/min; 95% confidence interval, 18-370 mL/min) compared with the youngest patients. The systemic absorption was biphasic. Absorption kinetics for ropivacaine (fractions absorbed: (F1, F2) and half-lives: (t(1/2),a1), t(1/2),a2) during the fast and slow absorption process: 0.27 +/- 0.08 and 0.77 +/- 0.12, respectively; 10.7 +/- 5.2 min and 248 +/- 64 min, respectively) were in the same range as for other long-acting local anesthetics. F1 was on average 0.11 (95% confidence interval, 0.002-0.22) higher in the youngest compared with the middle age group. Observed age-dependent pharmacokinetic differences do not likely influence the risk of systemic toxicity in the elderly after a single epidural dose of ropivacaine.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands. M.J.G.Simon@lumc.nl
authors.forename: Mischa J G
authors.initials: MJ
authors.lastname: Simon
authors.forename: Bernadette T
authors.initials: BT
authors.lastname: Veering
authors.forename: Arie A
authors.initials: AA
authors.lastname: Vletter
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stienstra
authors.forename: Jack W
authors.initials: JW
authors.lastname: van Kleef
authors.forename: Anton G L
authors.initials: AG
authors.lastname: Burm
mesh_terms: D000042:Absorption / Q000187:drug effects* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000577:Amides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000767:Anesthesia, Epidural / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000077212:Ropivacaine