Drugs online research references
Scand J Infect Dis Suppl. 1992;83:15-21.
Azithromycin pharmacokinetics and penetration to lymph.
Bergan T, Jorgensen NP, Olszewski W, Zhang Y.
Department of Microbiology, University of Oslo, Norway.
The study of pharmacokinetics of azithromycin and penetration to peripheral human lymph was carried out in 14 healthy male volunteers taking 1 g orally after overnight fasting. Samples were analyzed by microbiological assay. The mean peak concentrations were 0.82 +/- 0.23 mg/l after 1.7 +/- 0.5 h in serum and 0.22 +/- 0.07 mg/l after 3.1 h in lymph. Nine of the 14 subjects showed a second and lower serum peak indicating the existence of enterohepatic circulation. The total areas under the serum concentrations curves (AUCs) till infinity were 7.9 +/- 3.1 mg. h/l compared to 4.4 +/- 1.2 mg.h/l in lymph. The mean lymph AUC was 68.1 +/- 20.7% of the serum AUC indicating a penetration ratio of 0.68. However, the actual amounts penetrating the tissues were much higher than this ratio suggests. Thus, after 6 h 81% of the drug was within the tissue compartment and after 120 h, 63% of the azithromycin was still present in the tissue compartment. The urinary recovery of azithromycin was 14.7 +/- 7.7% during the first 48 h. The serum curves and lymph curves displayed a distinctly slower phase of elimination after 12 h. The mean serum half-life was 5.4 +/- 3.4 h during the first 12 h (after the peak), whereas the value was 44.2 +/- 10.1 h during the interval 12-120 h. The corresponding half-life values for the peripheral lymph were 5.4 +/- 2.2 h and 50.8 +/- 11.6 h. Azithromycin possesses key pharmacokinetic properties that are prerequisites for a convenient once-daily dosage schedule which may improve patient compliance.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1336891&dopt=Abstract
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J Antimicrob Chemother. 1992 Oct;30(4):497-507.
Potentiation of azithromycin activity against Escherichia coli by human serum ultrafiltrate.
Pruul H, McDonald PJ.
Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, Australia.
In this study we investigated the influence of serum ultrafiltrate on the activities of azithromycin, other macrolides and unrelated antibiotics against Escherichia coli. In the presence of serum ultrafiltrate the MIC of azithromycin was decreased by 10-fold. The activities of erythromycin and roxithromycin were also enhanced, although to a lesser extent. The potentiation of activity was inhibited by divalent cations and by pre-treatment of the ultrafiltrate with trypsin. Potentiation of azithromycin activity was associated with a pH-independent, early increase in bactericidal activity and inhibition of bacterial metabolism. We postulate that low molecular weight proteinaceous components of normal human serum interact with azithromycin and other macrolides to alter the susceptibility of Gram-negative bacteria to the antibiotics, possibly through increased macrolide penetration across the bacterial cell membrane permeability barriers.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1337068&dopt=Abstract
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J Mol Neurosci. 2003;20(3):267-75.
Drug discovery targeted to the Alzheimer's APP mRNA 5'-untranslated region: the action of paroxetine and dimercaptopropanol.
Payton S, Cahill CM, Randall JD, Gullans SR, Rogers JT.
Genetics and Aging Research Unit, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, USA.
We screened for drugs that specifically interact with the 5'-untranslated region of the mRNA encoding the Alzheimer's amyloid precursor protein (APP). Our goal was to use newly discovered APP 5' UTR directed compounds to limit amyloid-beta (Abeta)-peptide output in cell culture systems. The APP 5' UTR folds into a stable RNA secondary structure (Gibbs free energy: DeltaG = -54.9 kcal/mol) and is an important regulator of the amount of APP translated in response to IL-1 (Nilsson et al., 1998; Rogers et al., 1999) and iron (Rogers et al., 2002). Seventeen drug "hits" were identified from a library of 1,200 FDA preapproved drugs (Rogers et al., 2002). Six of the original 17 compounds were validated for their capacity to suppress reporter gene expression in stable neuroblastoma transfectants expressing the dicistronic reporter construct shown in Fig. 2. These six leads suppressed APP 5' UTR driven luciferase translation while causing no effect on the translation of dicistronic GFP gene translated from a viral IRES (negative control to ensure specificity during drug screens). In this report, we show that paroxetine (serotonin reuptake blocker) and dimercaptopropanol (Hg chelator) exerted significant effects on APP expression (steady-state levels of APP), whereas Azithromycin altered APP processing. None of these three compounds altered APLP-1 expression. In the future, we will identify further novel compounds that influence Abeta levels, either via translation inhibition or by changing the activity of proteins coupled between APP translation and APP processing.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14501007&dopt=Abstract
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