Drugs online research references
iupui.edu
Pimozide is often coprescribed with serotonin reuptake inhibitor (SSRI) antidepressants to treat depression in patients with Tourette's syndrome. In human liver microsomes (HLMs), the inhibition of the primary route of pimozide metabolism, N-dealkylation to 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one (DHPBI), by four SSRIs (fluoxetine, sertraline, paroxetine, and fluvoxamine) and azithromycin was tested. Inhibition constants (K(i) values) were estimated from Dixon plots (three HLMs for each inhibitor) using the appropriate enzyme inhibition model by nonlinear regression. At 10 microM paroxetine, sertraline, fluoxetine, or fluvoxamine, the formation of DHPBI from pimozide (10 microM) in HLMs was inhibited by an average (three HLMs) of 7%, 7.7%, 8%, and 16%, respectively, whereas this inhibition did not exceed 55% at the maximum concentrations (100 microM) of the SSRIs tested. Azithromycin had negligible effect on pimozide (10 microM) N-dealkylation (19% at 100 microM azithromycin). These inhibition data were compared with ketoconazole, which was included as a positive control of CYP3A inhibition. At 0.1 microM and 0.5 microM ketoconazole, the formation of DHPBI from 10 microM pimozide was inhibited by 32% and 62%, respectively. The K(i) values (+/- SD) of ketoconazole, sertraline, fluvoxamine, azithromycin, fluoxetine, and paroxetine were 0.07 microM, 89 +/- 44 microM, 89 +/- 24 microM, 103 +/- 52 microM, 117 +/- 27 microM, and 129 +/- 33 microM, respectively. These values are least 100-fold higher than the expected plasma concentrations after the usual daily doses of the SSRIs and azithromycin, suggesting that coadministration of SSRIs and azithromycin are unlikely to markedly diminish the elimination of pimozide in patients. However, in vivo predictions from in vitro data are not always perfect. In vivo, the SSRIs or azithromycin may concentrate in the liver relative to plasma. In addition, the possibility that these drugs could alter pimozide disposition through effects on transport proteins or via promoter repression cannot be ruled out.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11910261&dopt=Abstract
word match zithromax online literature
pfizer.com
The comparative safety of azithromycin was assessed in adult patients (> or =12 years) with community-acquired respiratory tract infections. Of 3229 patients evaluated, 1616 received azithromycin 500 mg once daily for 3 days and 1613 received standard regimens of amoxycillin, amoxycillin/clavulanic acid, cefaclor, clarithromycin, or roxithromycin. A similar incidence of treatment-related adverse events occurred with azithromycin (10.3%) and comparators (11.5%). Significantly fewer patients were withdrawn from azithromycin than comparator treatment (0.4 versus 2.1%; P=0.0001). Most adverse events were mild/moderate in intensity and affected the gastrointestinal system. Azithromycin was as well tolerated as other antibiotics commonly used for bacterial infections in adults.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11932140&dopt=Abstract
word match zithromax online literature
kcl.ac.uk
OBJECTIVE: To study the emergence of macrolide resistance in throat flora following treatment with clarithromycin or azithromycin. METHODS: Throat samples were collected before and after treatment and plated as a lawn on Columbia blood agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin and azithromycin were determined against isolates of distinct morphology with erythromycin E test MIC results equal to or greater than 2 mg/L. Polymerase chain reaction techniques were used to determine the genetic mechanisms of resistance. RESULTS: There were 749 resistant isolates of which 474 (63%) were streptococci. Only a quarter of the patients had no resistant streptococci before treatment started. There were increases in the numbers of resistant isolates and in the number of patients carrying a resistant flora during and after treatment. The most common genes identified were mefA/E in isolates with low-level resistance and ermA/M in isolates with high-level resistance. CONCLUSIONS: There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11952721&dopt=Abstract
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