Pharmacokinetics and pharmacodynamics of oral and intravenous cefetamet in dog.

The pharmacokinetic (PK) and pharmacodynamic (PD) properties of intravenously (IV) administered cefetamet-Na and per os (PO) administered cefetamet pivoxil were investigated in eighteen healthy dogs at three different dose levels. The three doses for IV cefetamet-Na were 95, 190 and 380 mg, while those for oral cefetamet pivoxil were 125, 250 and 500 mg (both equivalent to 90, 180 and 360 mg of cefetamet). An efficacy predictor, measured as the ratios of the time that the concentration of the free drug is over the MIC90 (T > MIC90) and the dosing interval (f% T > MIC90) of IV and PO administration were calculated. The PK parameters' maximum concentration (C max), half-life (t 1/2) and area under the curve (AUC0-t ) after three IV doses were 42.85 ± 11.79 µg/mL, 1.66 ± 0.36 h and 80.10 ± 28.92 mg h/L (95 mg); 93.50 ± 30.51 µg/mL, 1.47 ± 0.13 h and 1.47 ± 0.13 mg h/L (190 mg); 185.74 ± 113.83 µg/mL, 1.60 ± 0.38 h and 263.20 ± 73.27 mg h/L (380 mg). After PO administration, the C max, t 1/2 and AUC0-t at three doses were 9.25 ± 1.02 µg/mL, 1.79 ± 0.50 h and 31.90 ± 4.76 mg h/L (125 mg); 9.75 ± 1.77 µg/mL, 1.93 ± 0.65 h and 42.69 ± 8.93 mg h/L (250 mg); 15.55 ± 6.65 µg/mL, 2.02 ± 0.54 h, and 68.72 ± 24.11 mg h/L (500 mg). The IV f% T > MIC90 was greater than PO f% T > MIC90 when MIC90 was within the range of 0.25-256 mg/L.

A biological perspective of CSF lipids as surrogate markers for cognitive status in HIV.

The development and application of biomarkers to neurodegenerative diseases has become increasingly important in clinical practice and therapeutic trials. While substantial progress has been made at the basic science level in understanding the pathophysiology of HIV-Associated Neurocognitive Disorders (HAND), there are significant limitations in our current ability to predict the onset or trajectory of disease, and to accurately determine the effects of therapeutic interventions. Thus, the development of objective biomarkers is critical to further our understanding and treatment of HAND. In recent years, biomarker discovery efforts have largely been driven forward through the implementation of multiple "omics" approaches that include (but are not restricted to): Lipidomics, proteomics, metabolomics, genomics, transcriptomics, and advances in brain imaging approaches such as functional connectomics. In this paper we summarize our progress to date on lipidomic approaches to biomarker discovery, discuss how these data have influenced basic research on the neuropathology of HAND, and implications for the development of therapeutics that target metabolic pathways involved in lipid handling.