Diffusion of n-butyl-p-aminobenzoate (BAB), lidocaine and bupivacaine through the human dura-arachnoid mater in vitro

Introduction: Epidural administration of a suspension of n-butyl-p-aminoben zoate (BAB) to humans resulted in a selective, ultra-long lasting sensory b lock without motor function impairment. The absence of motor block was attr ibuted to 'spatial' confinement of active concentrations of dissolved BAB w ithin the epidural space. This study was designed to investigate the diffus ion of BAB through the human dura-arachnoid membrane in vitro relative to l idocaine and bupivacaine and to quantify the influence of the composition o f the suspension formulation on this flux. Materials and methods: Human dur a-arachnoid specimens were mounted between the donor and the receiver compa rtment of a diffusion cell. Five concentrations of BAB, lidocaine and bupiv acaine in phosphate-buffered saline, pH 7.4, were added to the donor compar tment and the increase of the concentration of the agent in time in the rec eiver compartment was measured by automated UV-spectrometry. Fluxes and per meabilities were calculated. The influence of pH, polysorbate 80 (PS 80) an d polyethylene glycol 3350 (PEG 3350) on the flux of BAB in solution and in suspension formulations were analyzed. Results: The flux of both lidocaine and bupivacaine at pH 4 was considerably smaller than at pH 7.4. Permeabil ities decreased in the order bupivacaine> lidocaine much greater than BAB a nd at the level T12>T1. PS 80 at concentrations exceeding 0.025 mg/ml and P EG 3350 decreased the flux of BAB from BAB-solutions. Used in the preparati on of the suspension, PS 80 and PEG 3350 did significantly reduce the perme ability. Discussion: The results of this study are consistent with the hypo thesis that the selective action of epidurally applied BAB suspension can b e attributed to the spatial confinement of active BAB-concentrations within the epidural space. Additives used in the preparation of the aqueous suspe nsion formulation may substantially influence the local pharmacokinetics an d by that the pharmacodynamic effects. (C) 2000 Elsevier Science B;V. All r ights reserved.