Pharmacokinetics of Ceftriaxone in skin following iontophoretic administration in a rabbit model

The fight against bacterial infection represents one of the high points of modern medicine. The development of antibiotics in the 1940s offered physicians a powerful tool against bacterial infections that has saved lives of millions of people.;Bacterial infection can be caused by a wide range of bacteria, resulting in mild to life-threatening illness such as bacterial meningitis that requires immediate intervention.;Ceftriaxone is often used as antibiotic in treatment of various bacterial infections such as lower respiratory tract infection, skin and skin structure infections, meningitis etc.;Ceftriaxone is commercially available as injection form to be administered by the IV and IM routes. The main purpose of my thesis is to evaluate the feasibility of trans-dermal delivery of the drug by means of iontophoresis. Iontophoresis is a method of transferring substances to and from the body for the therapeutic or diagnostic purposes by applying an electric potential to enhance their movement across biological membrane. If Iontophoresis allow Ceftriaxone concentration in dermis extracellular fluid to reach concentrations above the MIC, then there may be chances that ceftriaxone may have antibacterial activities in skin without the necessity of systemic administrations. The dermis concentration of Ceftriaoxne was measured by microdialysis. There are many techniques available to monitor tissue site concentration in vivo, among which Micro-dialysis is the only one to allow sequential sampling over time. Other techniques like biopsy sample or traditional concentration measurement in bodily secretions usually only yield a limited number of time points.;Microdialysis is a technique which is semi-invasive and used to determine the chemical components of the fluid in the extracellular spaces of tissue. It has been employed for the in vivo measurement of antibiotic tissue concentration. Micro-dialysis satisfies regulatory requirements for pharmacokinetic distribution studies due to selective access to the target site for most anti-infective drug. So it has become a reference technique for tissue distribution studies.;The HPLC method selected for the determination of ceftriaxone in plasma and micro-dialysis samples used a reversed phase C18 column with a flow rate of 1 ml/min and a detection wavelength of 270 nm. Water:Methanol:Trimethylamine(650:350:4) (pH 3) was used as mobile phase for both microdialysis and plasma samples. The retention time was 4.53 minutes. The calibration curve was liner for the micro dialysis samples in the range 0.03-10mug/ml. The lower limit of quantification was 0.03mug for micro dialysis samples.;Three pathogen free female New Zealand albino rabbits were selected to study the kinetics of ceftriaxone. The rabbit was tranquilized and micro-dialysis probes were implanted. Retrodialysis was performed at the start of the each experiment to assess probe recovery. Recovery was used to correct the dialysate concentration to reflect the actual interstitial fluid concentration. After that probe was perfused with lactated Ringer's solution and ceftriaxone was administrated by means of iontophoresis. The experiment was repeated three time in each rabbit at different current densities (100, 200, and 300 uA/cm2) in a randomized cross-over design.;The result shows that Iontophoretic administration of ceftriaxone is possible in rabbit skin. Maximum concentration of ceftriaxone reaches in 45 to 60 minutes in one hour iontophoretic application of ceftriaxone.