In a four-way cross-over study, the absolute bioavailability of cefixime was determined in 16 healthy volunteers. Each subject received a single 200-mg dose as an intravenous (IV) and oral solution, and 200-mg and 400-mg capsule doses of the drug. Blood and urine samples were collected for 24 hours after each dose. Cefixime was well tolerated after IV and oral doses of the drug and no serious drug-related adverse effects were observed. The maximal serum concentration (Cmax) of cefixime following the 200-mg oral solution and 200-mg and 400-mg capsule doses were 3.22, 2.92, and 4.84 micrograms/mL, respectively. Mean area under the serum concentration time curves (AUC) following the IV, 200-mg oral solution, and 200-mg and 400-mg capsule doses were 47.0, 26.0, 23.6, and 39.4 micrograms.hr/mL, respectively. Mean elimination half-life values of the drug were comparable after oral and IV doses, ranging from 3.2 to 3.5 hours. Based on serum AUC values, the absolute bioavailability of cefixime was 52.3%, 47.9%, and 40.2% after the 200-mg oral solution, 200-mg capsule and 400-mg capsule doses, respectively. Respective ratios based on 24-hour urinary recovery data were 44.7%, 41.7%, and 40.5%. Therefore, the results show that the percent of cefixime adsorbed after 200-mg and 400-mg oral doses was similar.
We report the use of technetium-99m sestamibi (MIBI) in a patient with multiple myeloma (MM) undergoing peripheral blood stem cell (PBSC) transplantation. MIBI is a radionuclide agent that is preferentially taken up by malignant tumors. Plain radiographs in a MM patient, taken prior to PBSC transplantation, showed a large right humeral lytic lesion that correlated with increased uptake of MIBI at the same location. MIBI uptake, demonstrating active MM bone disease, was also evident in areas which were normal on plain radiographs. Three months after PBSC transplant, the lytic lesion had healed by plain radiographs and repeat MIBI scan showed no uptake. MIBI scanning results have a positive correlation with plain radiographs, and more importantly, demonstrate active MM bone disease not yet detectable by plain radiographs. If MIBI proves more sensitive in the detection of MM bone disease than plain radiographs or bone scanning with traditional isotopes, it will have a significant role in the detection of early disease and in monitoring disease progression during and after therapy.
Generating molecular information in a clinically relevant time frame is the first hurdle to truly integrating precision medicine in health care. Reverse phase protein microarrays are being utilized in clinical trials for quantifying posttranslationally modified signal transduction proteins and cellular signaling pathways, allowing direct comparison of the activation state of proteins from multiple specimens, or individual patient specimens, within the same array. This technology provides diagnostic and therapeutic information critical to precision medicine. To enhance accessibility of this technology, two hurdles must be overcome: data normalization and data acquisition. Herein we describe an unamplified, dual-color signal detection methodology for reverse phase protein microarrays that allows multiplex, within spot data normalization, reduces data acquisition time, simplifies automated spot detection, and provides a stable signal output. This method utilizes Quantum Nanocrystal fluorophore labels (Qdot) substituted for organic fluorophores coupled with an imager (ArrayCAM) that captures images of the microarray rather than sequentially scanning the array. Streamlining and standardizing the data analysis steps with ArrayCAM high-resolution, dual mode chromogenic/fluorescent array imaging overcomes the data acquisition hurdle. The spot location and analysis algorithm provides certain parameter settings that can be tailored to the particular microarray type (fluorescent vs. colorimetric), resulting in greater than 99 % spot location sensitivity. The described method demonstrates equivalent sensitivity for a non-amplified Qdot immunoassay when using automated vs. manual immunostaining procedures.
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