Delivery of cefotaxime to the brain via intranasal administration.

The purpose of this study was to investigate the plausibility of delivery of cefotaxime to the brain via intranasal administration. In vitro permeation studies were carried out using Franz diffusion cells, and the effect of different concentrations of chitosan (0.1% w/v and 0.25% w/v) on drug permeation across the bovine olfactory mucosa was determined. Samples were collected from the receiver compartment at different time points and analyzed using HPLC. The amount of cefotaxime that permeated across the olfactory mucosa when 0.25% w/v of chitosan was used as a permeation enhancer was ~1.5- and ~2-fold higher at the end of the first hour and second hour, respectively, over control (29.56 ± 6.18 µg/cm(2)). There was no significant enhancement in drug permeation when 0.1% w/v chitosan was used as the permeation enhancer. Pharmacokinetic studies were carried out using Sprague-Dawley rats. Cefotaxime solution with 0.25% w/v chitosan (40 mg/kg) was administered intravenously (i.v.) to rats in groups 1 and 3 and intranasally to those in group 2 and 4. The time course of drug in the brain was investigated by performing microdialysis in rats of groups 1 and 2. Blood samples were withdrawn from rats in groups 3 and 4, and cefotaxime in plasma was analyzed using HPLC after extraction with a hydrochloric acid-chloroform:1-pentanol (3:1) and phosphate buffer solvent system. Pharmacokinetic parameters were calculated using the trapezoidal rule. The results imply that the drug levels attained in the brain following i.v. and intranasal administrations were comparable. These results suggest that intranasal administration of cefotaxime could be a potential method of delivering antibacterial agents because of it being noninvasive and patient compliant.

Denosumab Related Osteonecrosis of the Jaw with Spontaneous Necrosis of the Soft Palate: Report of a Life Threatening Case.

Bisphosphonates have been used for years in the treatment of patients with distant bony metastasis and in the prevention of osteoporosis. One of main side effects of these medications is the development of bisphosphonate related osteonecrosis of the jaw (BRONJ) in a small subset of patients. A new class of medications with a shorter half-life, known as receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, was introduced with the hopes of avoiding this side effect. However, reports of osteonecrosis of the jaw after the use of RANKL inhibitors have also been documented. We report on a patient who developed a life threatening osteonecrosis of the jaw with sepsis shortly after switching from a bisphosphonate to a RANKL inhibitor for osteoporosis treatment. This patient developed several soft tissue defects including spontaneous necrosis of the soft palate. To our knowledge this is the first time this presentation has been described.