AIMTo investigate the metabolic profile of roxithromycin in dogs and the effects of oral and intravenous administrations on the metabolism of roxithromycin.

METHODSLiquid chromatography-tandem mass spectrometry (LC-MSn) was used for separation and analysis of roxithromycin and its metabolites in dog bile after an oral dose or intravenous dose of roxithromycin. The metabolites were identified by comparisons of their mass spectra and LC behaviors with the references.

RESULTSTotally 13 metabolites were detected in dog bile, including N-demethylated derivatives, N, N-didemethylated derivatives, O-dealkylether derivatives, decladinose derivatives, and the geometric isomers of parent drug and its metabolites.

CONCLUSIONRoxithromycin underwent 4 metabolic pathways in which geometric isomerization and decladinose metabolism were found to be markedly different between the two administration routes.

Administration, Oral ; Animals ; Anti-Bacterial Agents ; administration & dosage ; metabolism ; Bile ; metabolism ; Biotransformation ; Chromatography, Liquid ; Dogs ; Injections, Intravenous ; Male ; Mass Spectrometry ; Roxithromycin ; administration & dosage ; metabolism

The relative bioavailability of roxithromycin dispersive tablet in healthy volunteers was evaluated in this study. Its concentration in plasma was detected by high performance liquid chromatography (HPLC) after twenty healthy male volunteers were given each a single dose of 300 mg roxithromycin. The experiment data were obtained using DAS programme. The values of Cmax were 10.16+/-1.46 and 10.34+/-1.66 microg x ml(-1) at 2.33+/-0.61 and 2.28+/-0.62 h respectively; of t1/2 were 9.00+/-1.58 and 8.68+/-1.66 h respectively; of AUC0-->Tn were 143.32 +/-25. 80 and 138.93+/-22. 49 microg x h x ml(-1) respectively; of AUC0-->infinity were 158.63+/-26.86 and 153.77+/-24.75 microg x h x ml(-1) for test and reference drugs. Relative bioavailability of the tested roxithromycin was 103.63%+/-14.04%. The result showed that the two dispersive tablets are bioequivalent.
Administration, Oral ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Humans ; Male ; Roxithromycin ; blood ; pharmacokinetics ; Tablets ; Therapeutic Equivalency ; Young Adult

A highly sensitive and specific method for the determination of roxithromycin in broiler tissues by LC/MS was developed and validated. A dichloromethane extract of the sample was separated on C18 reversed-phase column with acetonitrile-50 mM ammonium acetate (80:20, v/v) as the mobile phase and analyzed by LC/MS via atmospheric pressure ionization/electrospray ionization interface. The limit of detection and limit of quantitation were 1 ng/g and 5 ng/g. The method has been successfully applied to determine for roxithromycin in various tissues of broilers. Residue concentrations were associated with administered dose. At the termination of treatment, roxithromycin was found in all collected samples for both dose groups. Liver was detected to have the highest residual concentration of roxithromycin. Residue concentrations of roxithromycin were lower than its LOQ in all tissues from both dose groups 10 days after the treatment of roxithromycin mixed with drinking water at a dose rate of 15 mg/L or 60 mg/L to each broiler for 7 days.
Adipose Tissue/metabolism ; Animals ; Chickens/blood/*metabolism ; Chromatography, Liquid ; Drug Administration Schedule ; Intestine, Small/metabolism ; Kidney/metabolism ; Liver/metabolism ; Mass Spectrometry ; Molecular Structure ; Muscle, Skeletal/metabolism ; Roxithromycin/*administration&dosage/blood/chemistry/*pharmacokinetics ; Sensitivity and Specificity ; Skin/metabolism

This is a study of assessing the comparative bioavailability of roxithromycin produced by two companies in 36 healthy volunteers. On the basis of informed consent, 36 healthy male volunteers received each medicine at the roxithromycin dose of 150mg in a cross-over study. There was a 1-week washout period among the doses. Plasma concentrations of roxithromycin were monitored by an LC-MS/MS for over a period of 72 hours after administration. In this study, roxithromycin was generally well tolerated. After an oral administration of roxithromycin capsule, the pharmacokinetic parameters of roxithromycin, such as AUC(0-72 h) (66 076 microg x L x h(-1) and 70 334 microg x L x h(-1) for test and reference capsule, respectively) and AUC(0-infinity) (68 153 microg x L x h(-1) and 72 362 microg x L x h(-1)) were significantly similar. For test and reference capsule, the values of C(max) were 6 631.5 microg x L(-1) and 7 033.9 microg x L(-1) respectively, of T1/2 were 15.39 +/- 4.61 h and 16.06 +/- 5.56 h, and of T(max) were 1.3 +/- 0.9 h and 1.4 +/- 0.7 h respectively. The relative bioavailability F was 94.9% +/- 22.4% of tested formulation. The values of 90% confidence interval around the ratios (test/reference) (obtained by analysis of variance, ANOVA) were 88.3%-101.2% for C(max), 86.2%-98.9% for AUC(0-72) h, being within the predefined acceptable range for the conclusion of bioequivalence. The results of statistical analysis suggest that the two formulations be bioequivalent.
Adult ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; methods ; Cross-Over Studies ; Humans ; Male ; Roxithromycin ; administration & dosage ; pharmacokinetics ; Tablets ; Tandem Mass Spectrometry ; methods ; Young Adult

OBJECTIVE: Observe the therapeutic effect of low dose Roxithromycin in treating chronic sinusitis and further discuss the mechanism of Roxithromycin facile endothelial cell apoptosis. METHOD: All 47 patients who suffer chronic sinusitis at out-patient clinic from 2006. 10 to 2008. 03 were administered low dose Roxithromycin. Follow up all the patients and get polypi at 3-month and 6-month. AO/EB was employed to detect the apoptosis of endothelial cell. RESULT: At 3-month and 6-month the improvement of ventilation are 37.25 +/- 12.21, 63.15 +/- 22.78; Decrease of nasal discharge are 42.12 +/- 13.56, 74.45 +/- 28.79; alleviation of headache are 18.98 +/- 7. 66, 34.47 +/- 14.11; Improvement of olfactory are 21.23 +/- 8.41, 38.18 +/- 16.54; Apoptotic index are (39.54 +/- 6.86)% and (62.34 +/- 8.67)%, which are significantly different (P<0.05). CONCLUSION Low dose Roxithromycin has good long term curative effect in treating chronic sinusitis. Low dose Roxithromycin can greatly urge the apoptosis of endothelial cell.
Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Apoptosis ; Child ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Nasal Polyps ; complications ; drug therapy ; Roxithromycin ; administration & dosage ; therapeutic use ; Sinusitis ; complications ; drug therapy ; Young Adult