Spinal Disposition and Meningeal Permeability of Local Anesthetics

Abstract

The unexpected increase in CSF bioavailability with a decrease in absorption rate through meninges emphasizes the role of specific competitive clearance and distribution processes in the epidural space.

Cerebral kinetics of oxycodone in conscious sheep

“…Different factors such as molecular weight have been incorporated into the fitting of the relationship and found to improve the correlations seen. 28,29 A summary of the brain kinetics of different opioids is shown in Table 3 along with relevant physico-chemical parameters. With exception of methadone and LAAM, the proposed relationship applies for the opioids shown in Table 3.…”

Ex vivo and in vivo diffusion of ropivacaine through spinal meninges: Influence of absorption enhancers

“…Three competitive processes are driving the epidural disposition of drugs, i.e. transmeningeal uptake into intrathecal space, uptake into the systemic circulation and distribution into the epidural fat (Clement et al, 2004). Different mechanisms can modulate the balance of these processes.…”

“…[ 3 H]Mannitol used as hydrophilic radiotracer of paracellular passage (MW 182; specific activity 20 Ci/mmol; radiochemical purity 99%) was obtained from Sigma (St Louis, MO, USA). A mock cerebrospinal fluid (CSF) solution (NaCl 8.2 g/l, MgCl 2 ·6H 2 O 0.08 g/l, urea 0.2 g/l, glucose 0.7 g/l, CaCl 2 ·2H 2 O 0.3 g/l; pH = 7.38-7.42; 292-298 mOsm/l) was used as medium for the ex vivo experiment on isolated meninges and a Ringer's solution (NaCl 8.6 g/l, KCl 0.33 g/l, CaCl 2 ·2H 2 O 0.3 g/l, pH 7.0) was used as perfusion fluid during the microdialysis experiments (Clement et al, 2004). All other reagents were of analytical grade.…”

Population Pharmacokinetics of Amitriptyline After Intrathecal, Epidural, and Intravenous Administration in Sheep

“…The choice of EPI and IT doses of AMI used here was based on a target IT bioavailability of 10%, the mean value obtained for local anesthetics. 17,18 Chromatographic Analysis and Drug Assay…”