Drugs online research references
J Chemother. 2003 Aug;15(4):350-6.
Interaction of macrolides and ketolides with the phagocytic cell line PLB-985.
Abdelghaffar H, Soukri A, Babin-Chevaye C, Labro MT.
Faculte des Sciences 1, Ain Chock, BP 5366, Maarif, Casablanca, Morocco.
Interactions between antibacterial agents and polymorphonuclear neutrophils (PMNs) are a major focus of investigation. Owing to the variable drug susceptibility of PMNs from different individuals, in vitro studies require samples from large panels of healthy volunteers to reach statistical significance. Here, we used a phagocytic cell line, PLB-985, which can differentiate into mature PMNs in vitro, for the study of cellular interactions (drug uptake and antioxidant effects) of two macrolides (azithromycin and roxithromycin) and four ketolides [HMR 3004, HMR 3647 (telithromycin), HMR 3562 and HMR 3787]. The oxidative burst of differentiated (D) cells was inhibited by macrolides and ketolides. IC50% values (concentrations impairing the oxidative burst by 50%), determined after 30 min of incubation, were as follows for azithromycin, roxithromycin, HMR 3004, telithromycin, HMR 3562 and HMR 3787, respectively: 40, 39, 15, 23, 26, and 33 mg/l (fMLP stimulation) and 37, 86, 39, 43, 14, and 31 mg/l (PMA stimulation). These values were similar to those obtained with PMNs. Uptake of the two macrolides was significantly lower in non-differentiated (ND) cells than in D cells and PMNs. The cellular/extracellular (C/E) concentration ratios at 60 min for PMNs, D and ND PLB were respectively 67, 25 and 11 (roxithromycin) and 159, 137 and 48 (azithromycin). Ketolide uptake by ND-PLB was also significantly lower than that obtained with PMNs (C/E ratios at 60 min were about 75 versus 265 (HMR 3004), 36 vs 230 (telithromycin), 75 vs 235 (HMR 3562) and 20 vs 130 (HMR 3787). Although the active carrier system seemed to be present in ND cells, its activation pathway was not functional. Thus, the PLB-985 cell line is a good in vitro model for studying drug-PMN interactions. The use of ND and D cells may shed light on the nature and activation pathways of macrolide transport systems present on the PMN membrane.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12962363&dopt=Abstract
word match zithromax online literature
Kurume Med J. 2003;50(1-2):9-15.
Macrolide antibiotics directly reduce active oxygen generation by neutrophils in human peripheral blood.
Sugihara E, Koyanagi T, Niizeki T, Hirota N, Nagafuchi M, Yamada K, Kido Y, Ono N, Rikimaru T, Aizawa H.
Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
Since a "low-dose and long-term" administration of erythromycin (EM) was reported to be effective in patients with chronic respiratory diseases, including diffuse panbronchiolitis (DPB), the modulation of host defense responses by EM has attracted much attention. Despite considerable controversy, it was recently demonstrated that macrolides reduced neutrophil function. In this study, we investigated the effects of EM, a 14-membered ring macrolide, azithromycin (AZM), a 15-membered ring macrolide, and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil function in terms of active oxygen generation of neutrophils in the absence and presence of mononuclear cells in vitro. EM and AZM significantly suppressed active oxygen generation by neutrophils in the absence of mononuclear cells at low concentration (0.5 microgram/ml. p < 0.05). At the next step, to confirm that EM and AZM directly reduced active oxygen generation by neutrophils, we investigated whether mononuclear cells affected this effect of EM and AZM. In the presence of mononuclear cells pretreated with EM or AZM, both antibiotics suppressed active oxygen generation at concentrations ranging from 0.5 to 20 micrograms/ml. However, the inhibition rates induced by EM and AZM at low concentrations were not so different between the absence and the presence of mononuclear cells. These results indicated that EM and AZM have direct effects on the active oxygen generation by neutrophils and those effects that were not influenced by mononuclear cells. This inhibitory effect may be responsible for the therapeutic efficacy of these 14-membered and 15-membered ring macrolides in patients with DPB.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12971257&dopt=Abstract
word match zithromax online literature
J Pharm Biomed Anal. 2003 Sep 19;33(2):211-7.
LC determination of impurities in azithromycin tablets.
Miguel L, Barbas C.
Facultad de CC Experimentales y de la Salud. Universidad San Pablo-CEU, Urbanizacion Montepri;ncipe, Ctra. Boadilla del Monte, km 5,3-28668 Madrid, Spain.
A LC method with UV detection for determining azithromycin impurities in tablets as pharmaceutical form has been developed. It is to be employed in routine and stability tests. A linear gradient elution was employed starting with 47% A and 53% B to reach 28% A and 72% B at 48 min. Mobile phase A was KH2PO4 10 mM (H2O) at pH 7.00. B was a mixture methanol:acetonitrile 1:1 (v/v). UV detection was performed at 210 nm. The chromatographic column was Phenomenex Synergi MAX-RP 4 microm 250 x 460 mm kept at 50 degrees C. Six impurities were separated and identified and it was possible to quantify five out of the six with reasonable accuracy and precision.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12972086&dopt=Abstract
word match zithromax online literature
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