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na.amedd.army.mil

Initial field malaria prophylaxis trials with azithromycin revealed insufficient efficacy against falciparum malaria to develop azithromycin as a single agent. The objective of this in vitro study was to determine the best drug combination(s) to evaluate for future malaria treatment and prophylaxis field trials. In vitro, azithromycin was tested in combination with chloroquine against 10 representative Plasmodium falciparum isolates. Azithromycin was also assessed in combination with eight additional antimalarial agents against two or three multidrug-resistant P. falciparum isolates. Parasite susceptibility testing was carried out with a modification of the semiautomated microdilution technique. The incubation period was extended from the usual 48 h to 68 h. Fifty percent inhibitory concentrations (IC(50)s) were calculated for each drug alone and for drugs in fixed combinations of their respective IC(50)s (1:1, 3:1, 1:3, 4:1, 1:4, and 5:1). These data were used to calculate fractional inhibitory concentrations and isobolograms. Chloroquine-azithromycin studies revealed a range of activity from additive to synergistic interactions for the eight chloroquine-resistant isolates tested, while an additive response was seen for the two chloroquine-sensitive isolates. Quinine, tafenoquine, and primaquine were additive to synergistic with azithromycin, while dihydroartemisinin was additive with a trend toward antagonism. The remaining interactions appeared to be additive. These results suggest that a chloroquine-azithromycin combination should be evaluated for malaria prophylaxis and that a quinine-azithromycin combination should be evaluated for malaria treatment in areas of drug resistance.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12121927&dopt=Abstract

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Eur J Pharm Sci. 2002 Aug;16(3):175-84.
Characterization of azithromycin hydrates.

Gandhi R, Pillai O, Thilagavathi R, Gopalakrishnan B, Kaul CL, Panchagnula R.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar-160 062, Punjab, India.

Azithromycin (AZI) is a macrolide antibiotic with an expanded spectrum of activity that is commercially available as a dihydrate. This study was carried out to characterize hydrates of azithromycin. A commercial dihydrate sample was used to prepare monohydrate from water/ethanol (1:1) mixture. Hydrates were characterized using DSC, TGA, KFT, XRD, HSM, SEM and FT-IR. TGA showed that the commercial samples are dihydrate and the sample prepared from water/ethanol (1:1) was a monohydrate. Solubility studies revealed that monohydrate converted to dihydrate during solubility studies and as a result there was no significant difference in the equilibrium solubility of MH and DH. Thermal analysis under various conditions revealed that dehydration and melting took place simultaneously. Anhydrous AZI was found to be hygroscopic and converted to DH on storing at room temperature. Molecular modeling studies revealed the probable sites of attachment of water molecules to AZI.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12128172&dopt=Abstract

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ic.ac.uk

The ex vivo cytokine response to lipopolysaccharide (LPS) of whole blood from patients with typhoid fever was investigated. Tumor necrosis factor (TNF)-alpha release by LPS-stimulated blood was found to be lower during acute typhoid fever than after a course of antimicrobial therapy (P<or=.001). Ex vivo interleukin (IL)-1beta, but not IL-1 receptor antagonist, release was also depressed during the acute stage of typhoid fever. Low ex vivo production of TNF-alpha was associated with delayed recovery. No association was found between the TNFA-308 promoter polymorphism and LPS-induced TNF-alpha release, either during an active infection or after treatment. In acute typhoid fever, the ability of peripheral blood leukocytes to release proinflammatory cytokines in response to an inflammatory stimulus is depressed, and this may contribute to delayed recovery following antibiotic treatment.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12134261&dopt=Abstract

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