Determination of lamivudine and zidovudine permeability using a different ex vivo method in Franz cells

摘要

Introduction: The major processes that control the absorption of orally administered drugs are dissolution and gastrointestinal permeation. These processes depend on two main properties: solubility and permeability. Based on these characteristics, the Biopharmaceutical Classification System (BCS) was proposed as a tool to assist in biowaiver and bioavailability prediction of drugs. Methods: The purpose of the present study was to evaluate the permeability of lamivudine (3TC) and zidovudine (AZT) using a different ex vivo method in Franz cells. A segment of jejunum was inserted in a Franz cells apparatus, in order to assess drug permeability in the apical-basolateral (A-B) and basolateral-apical (B-A) directions. Each drug was added to the donor chamber, collected from the acceptor chamber and analyzed by HPLC. Fluorescein (FLU) and metoprolol (METO) were used as low and high permeability markers, respectively. Results: The apparent permeability (Papp) results for the A-B direction were: Papp FLU A-B=0.54×10-4cm·s-1, Papp METO A-B=7.99×10-4cm·s-1, Papp 3TC A-B=4.58×10-4cm·s-1 and Papp AZT A-B=5.34×10-4cm·s-1. For the B-A direction, the Papp results were: Papp FLU B-A=0.56×10-4cm·s-1, Papp METO B-A=0.25×10-4cm·s-1, Papp 3TC B-A=0.24×10-4cm·s-1 and Papp AZT B-A=0.19×10-4cm·s-1. Discussion: For the A-B direction, the Papp results of fluorescein and metoprolol show low and high permeability, respectively, indicating that the membranes were appropriate for permeability studies. For the A-B direction, the Papp results of 3TC and AZT suggest that these antiretroviral drugs have permeability values close to metoprolol. Nevertheless, for the B-A direction the Papp results do not suggest efflux mechanism for any of the drugs. Thereby, the different ex vivo methods using Franz cells can be successfully applied in drug permeability studies, in particular for drug biopharmaceutical classification.