Pharmacokinetics of Cefuroxime(CFX) in skin following iontophoresis in rabbit

The main purpose of this study is to evaluate the effect of different electric current densities on iontophoretic delivery of Cefuroxime across rabbit skin in vivo via microdialysis sampling technique and to estimate skin pharmacokinetic parameters. Cefuroxime was dissolved in a mixture of glycerine and water to minimize damage to skin, as previously reported by N.Goel in his thesis.;Cefuroxime (CFX) is a second generation cephalosporin active against a wide range of aerobic and anaerobic gram-positive and gram-negative organisms. It is recommended to treat skin bacterial infections. High oral doses of CFX are required to achieve Minimum Inhibitory Concentration (MIC) at the site of infection that may localized in a very small area of skin. Therefore, the feasibility to administer CFX by iontophoresis was explored in a rabbit model by measuring dennis concentrations by microdialysis. Previous in-vitro studies had shown that CFX is stable under anodic current at the same current densities used in-vivo.;The HPLC method used for the quantification of Cefuxome is a modified reverse phase HPLC assay method. The HPLC parameters are 1ml/min isocratic flow rate, U.V detector wavelength of 280 nm (lambdamax for Cefuroxime), sample injection volume of 10mul, running time of 7 minutes and a waters C18 column. The mobile phase consisted of 30:70 (v/v) of methanol: 50mM phosphate buffer (pH 5.0) containing 7mM triethylamine (TEA).;Two microdialysis probes with a 1 cm dialysis membrane made of tubular polyacrylonitrile (molecular weight cutoff; 50 KDa) were inserted into the upper dorsal shaved skin of tranquilized female, pathogen-free New Zealand albino rabbits. After one hour, an iontophoresis cartridge consisting of a stainless steel electrode and a non-woven polypropylene pad with a surface area of 3.14 cm² was placed on top of one probe. The cartridge pad was previously soaked with 0.4 mL of 45mg/mL CFX in a 60:40 glycerin/water solution. Iontophoresis was performed at constant current density of 100, 200, or 300 muA/cm² for 60 minutes on 3 rabbits according to a cross-over design. Dialysate samples were collected every 10 min for 3 hours (flow rate: 2 muL/min) and analyzed for CFX via a validated HPLC assay. Retrodialysis was performed at the other site to estimate the recovery factor.;Rabbit well tolerated the method as no skin damage was observed. In-vivo retrodialysis recovery was 54.6 +/- 6.8%. CFX skin exposure increased proportionally with current density. AUCs were 615 +/- 39, 4963 +/- 184, and 7609 +/- 279 mg/L*min for the 100, 200, and 300 muA/cm² respectively and Cmax were 1.2 +/- 0.40, 7.5 +/- 0.56, and 12.5 +/- 1.18 mg/L respectively.;Therapeutically effective skin concentrations of CFX were obtained by anodic iontophoresis. Specifically, CFX skin concentrations raised above MIC for staphylococcus aureus and streptococcus pyogenes (0.5--2.0mug/mL) immediately after the application of the lowest current density and remained above it for at least 1.5 hours after the discontinuation of current.