Roxithromycin: Difference between revisions

Roxithromycin
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy; category	? (USA) ; B1 (Aus);
ATC code	J01FA06 (WHO) ;
Pharmacokinetic data
Metabolism	Liver, peak concentration averaging 2 hours after ingestion.
Elimination half-life	12 hours
Identifiers
	IUPAC name (3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-d-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-(2-methoxyethoxymethoxyimino)-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecan-2-one;
CAS Number	80214-83-1 ;
PubChem CID	6915744;
DrugBank	DB00778 ;
ChemSpider	5291557 ;
UNII	21KOF230FA;
KEGG	D01710 ;
ChEBI	CHEBI:48935 ;
ChEMBL	ChEMBL1214185 ;
CompTox Dashboard (EPA)	DTXSID8041117 ;
ECHA InfoCard	100.121.308
Chemical and physical data
Formula	C41H76N2O15
Molar mass	837.047 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C3O[C@H](CC)[C@](O)(C)[C@H](O)[C@H](\C(=N\OCOCCOC)[C@H](C)C[C@](O)(C)[C@H](O[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O)[C@H]([C@H](O[C@@H]2O[C@H]([C@H](O)[C@](OC)(C2)C)C)[C@H]3C)C)C;
	InChI InChI=1S/C41H76N2O15/c1-15-29-41(10,49)34(45)24(4)31(42-53-21-52-17-16-50-13)22(2)19-39(8,48)36(58-38-32(44)28(43(11)12)18-23(3)54-38)25(5)33(26(6)37(47)56-29)57-30-20-40(9,51-14)35(46)27(7)55-30/h22-30,32-36,38,44-46,48-49H,15-21H2,1-14H3/b42-31+/t22-,23-,24+,25+,26-,27+,28+,29-,30+,32-,33+,34-,35+,36-,38+,39-,40-,41-/m1/s1 ; Key:RXZBMPWDPOLZGW-XMRMVWPWSA-N ;
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Revision as of 23:54, 30 May 2012

Roxithromycin is a semi-synthetic macrolide antibiotic. It is used to treat respiratory tract, urinary and soft tissue infections. Roxithromycin is derived from erythromycin, containing the same 14-membered lactone ring. However, an N-oxime side chain is attached to the lactone ring. It is also currently undergoing clinical trials for the treatment of male-pattern hair loss.^[1]

Roxithromycin is available under several brandnames, for example, Xthrocin, Roxl-150, Roxo, Surlid, Rulide, Biaxsig, Roxar, Roximycin, Roxomycin, Rulid, Tirabicin and Coroxin. Roxithromycin is not available in the United States. Roxithromycin has also been tested to possess antimalarial activity.

History

German pharmaceutical company Hoechst Uclaf brought out roxithromycin in 1987.

Available forms

Roxithromycin is commonly available as tablets or oral suspension.

Mechanism of action

Roxithromycin prevents bacteria from growing, by interfering with their protein synthesis. Roxithromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides. Roxithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Legionella pneumophila.

Pharmacokinetics

When taken before a meal, roxithromycin is very rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, roxithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of roxithromycin are released.

Metabolism

Only a small portion of roxithromycin is metabolised. Most of roxithromycin is secreted unchanged into the bile and some in expired air. Under 10% is excreted into the urine. Roxithromycin's half-life is 12 hours.

Side effects

Most common side effects are gastrointestinal; diarrhoea, nausea, abdominal pain and vomiting. Less common side effects include central or peripheral nervous system events such as headaches, dizziness, vertigo, and also the rarely seen rashes, abnormal liver function values and alteration in senses of smell and taste.

Drug interactions

Roxithromycin has fewer interactions than erythromycin as it has a lower affinity for cytochrome P450.

Roxithromycin does not interact with hormonal contraceptives, prednisolone, carbamazepine, ranitidine or antacids.

When roxithromycin is administered with theophylline, some studies have shown an increase in the plasma concentration of theophylline. A change in dosage is usually not required but patients with high levels of theophylline at the start of the treatment should have their plasma levels monitored.

Roxithromycin appears to interact with warfarin. This is shown by an increase in prothrombin time (international normalised ratio [INR]) in patients taking roxithromycin and warfarin concurrently. As a consequence, severe bleeding episodes have occurred.

Drug Dosage

Adults: 150 mg twice in a day, 30 minutes before meals or 2 hours after. For children, it is 2.5 - 5.0 mg/kg of body weight, given in two divided doses per day. ^[2] Mode of Administration- Oral.

References

^ "The Effect of 0.5% Roxithromycin Lotion for Androgenetic Alopecia - ClinicalTrials.gov". Retrieved 2007-09-22.
^ Medical pharmacology, Ch.-54, ISBN-81_8448_085_7

[1] "The Effect of 0.5% Roxithromycin Lotion for Androgenetic Alopecia - ClinicalTrials.gov". Retrieved 2007-09-22.

[2] Medical pharmacology, Ch.-54, ISBN-81_8448_085_7

[1]

[2]

@@ Line 83: / Line 83: @@
 <ref>Medical pharmacology, Ch.-54, ISBN-81_8448_085_7</ref>
 Mode of Administration- Oral.
-==Assay of Roxithromycin<ref>Analytical Method development by Liquid Chromatography, ISBN 978-3-8443-2869-1, LAP LAMBERT Academic Publishing GmbH & Co. KG, Germany. Published on 25-11-2011.</ref>==
-Stability of roxithromycin was studied by Wei Zhenping ''et al.''<ref>Wei Zhenping and Bi Dianzhou, A Comparative Study on the Stability of Roxithromycin in Different pH Solutions by Colorimetry, TLC and HPLC, Journal of Chinese Pharmaceutical Sciences 2000, 9 (4), 204-207.</ref> in solutions of different pH values were determined separately by colorimetry, TLC and HPLC.
-Oh-Seung Kwon ''et al.''<ref>Oh-Seung Kwon, Hey-Jung Kim, Heesoo Pyo and Youn Bok Chung, Bioequivalence assessment of Roxithromycin Tablets in healthy Korean volunteers, The Journal of Applied Pharmacology, 2006, 14, 50-55.</ref>  evaluated the bioequivalency between different brands of Roxithromycin Tablets administered to healthy Korean male volunteers using HPLC with fluorescence detector.
-The reversed-phase (RP) chromatographic behaviour of the macrolide antibiotics clarithromycin (Clari) and roxithromycin (Roxi) was extensively studied by A. Pappa-louisi ''et al.''<ref>A. Pappa-louisi, p. Agrafiotou, g. Zissopoulou, p. Liatsi, Influence of temperature and mobile phase composition on retention properties of the macrolide antibiotics clarithromycin and roxithromycin in reversed-phase liquid chromatography, BAÜ Fen Bil. Enst. Dergisi, 2002. 4.2, 17-19.</ref>  as a function of mobile phase composition - modified with one, two or three of organic solvents - and column temperature.
-A rapid and sensitive reverse phase high performance liquid chromatographic method with UV detection was developed by Prafulla Sahu ''et al.''<ref>Prafulla Kumar Sahu*, K.Ravi Sankar, M.Mathrusri Annapurna, Reverse phase high performance liquid chromatographic method for the analysis of Roxithromycin in bulk and pharmaceutical dosage forms”, Analytical Chemistry: An Indian Journal, 2009, 8(1).</ref> for the determination of Roxithromycin present in bulk and pharmaceutical dosage forms.
-A selective HPLC method with fluorescence detection for the determination of roxithromycin (ROX) in human plasma was described by Franciszek K. Główka et al.<ref>Franciszek K. Główka and Marta Karaźniewicz-Łada, Determination of roxithromycin in human plasma by HPLC with fluorescence and UV absorbance detection: Application to a pharmacokinetic study, Journal of Chromatography B, Volume 852, Issues 1-2, 1 June 2007, Pages 669-673.</ref> After solid-phase extraction (SPE), ROX and erythromycin (internal standard, I.S.) were derivatized by treatment with 9-fluorenylmethyl chloroformate (FMOC-Cl). Optimal resolution of fluorescence derivatives of ROX and I.S. was obtained during one analytical run using reversed phase, C18 column. The mobile phase was composed of potassium dihydrogenphosphate solution, pH 7.5 and acetonitrile. Fluorescence of the compounds was measured at the maximum excitation, 255&nbsp;nm and emission, 313&nbsp;nm, of ROX derivatives.
-A method for the determination of Roxithromycin in the flounder muscle by LC–MS was developed by Jong-hwan Lim et al.<ref>Jong-hwan Lim, Beom-su Jang, Rae-kyung Lee, Seung-chun Park and Hyo-in Yun, Determination of roxithromycin residues in the flounder muscle with electrospray liquid chromatography–mass spectrometry, Journal of Chromatography B: Biomedical Sciences and Applications, Volume 746, Issue 2, 15 September 2000, Pages 219-225.</ref> 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.
-Jin Sun ''et al.''<ref>Jin Sun, Tianhong Zhang, Feng Qiu, Yu Liu, Jingling Tang, Haihua Huang and Zhonggui He, Impact of pharmaceutical dosage forms on the pharmacokinetics of roxithromycin in healthy human volunteers, Journal of Antimicrobial Chemotherapy, 2011, 55, 5, 796-799.</ref>  described the impact of pharmaceutical dosage forms on the pharmacokinetics of roxithromycin in healthy human volunteers and characterization of roxithromycin degradation in simulated gastric fluid and simulated intestinal fluid using high performance liquid chromatography (HPLC)-tandem MS.
-A stability indicating reverse phase high performance liquid chromatographic  method is developed by Dhiraj S. Nikam ''et al.''<ref>Dhiraj S. Nikam, Swapnil C. Aswale, Stability indicating RP-HPLC method for simultaneous   estimation of ambroxol hydrochloride and roxithromycin in bulk and tablet dosage form, International Journal of Pharmaceutical Research and Development, 2010, 2, 10.</ref>  for simultaneous estimation of  ambroxol hydrochloride and roxithromycin in bulk and pharmaceutical formulation using water: acetonitrile: orthophosphoric acid (50:50:0.1) as a mobile phase. Detection was carried out at 210&nbsp;nm.
-An isocratic liquid chromatographic method has been developed by H. K. Chepkwony ''et al.''<ref>H. K. Chepkwony, F. N. Kamau, E. Rodriguez, E. Roets and J. Hoogmartens, Isocratic liquid chromatographic method for the analysis of roxithromycin and structurally related substances in bulk samples, Chromatographia, Volume 54, Numbers 11-12, 725-729.</ref>  for the analysis of bulk samples of Roxithromycin using acetonitrile-2.0M (NH4)2HPO4, pH 6.4-water, 25∶30∶45, (v/v) as mobile phase detection was by UV absorbance at 215&nbsp;nm. Sufficient separation of roxithromycin from its homolog containing one more methyleneoxy group (roxithromycin G) and from other related substances was achieved.
-Valéria de Oliveira ''et al.''<ref>Valéria de Oliveira; Ana Maria Bergold; Elfrides Eva Scherman Schapoval, High-Performance Liquid Chromatographic Determination of Roxithromycin in Tablets, Analytical Letters, 1996, 29, 13, 2377–2382.</ref>  described a High-Performance Liquid Chromatographic method for the determination of Roxithromycin in Tablets using 0.067 M phosphate buffer, pH 4.0 and methanol (65:35) as mobile phase and UV detection at 210&nbsp;nm.
-A liquid chromatography–mass spectrometry (LC–MS) method for the determination of roxithromycin in rat lung tissue is described by Peng Wang et al.<ref>Peng Wang, Meiling Qi, and Xin Jin, Determination of roxithromycin in rat lung tissue by liquid chromatography–mass spectrometry, Journal of Pharmaceutical and Biomedical Analysis, Volume 39, Issues 3-4, 15 September 2005, Pages 618-623.</ref>
-Chen Nai-jiang ''et al.''<ref>Chen Nai-jiang and Zhang Hong, HPLC-ELSD method for content determination of Roxithromycin, Chinese Journal of Antibiotics, 2009, doi: CNKI:SUN:ZKSS.0.2009-05-012.</ref>  described a HPLC-ELSD method for content determination of Roxithromycinusing methanol-0.2% trifluoroacetic acid(TFA) solution(50:50)(pH was adjusted to 6.5 with triethylamine) as mobile phase at room temperature and ELSD as detector.
-Dafang Zhong ''et al.''<ref>Dafang Zhong, Xueqing Li, Aimin Wang, Youjun Xu and Shuodong Wu, Identification of the Metabolites of Roxithromycin in Humans, Drug Metabolism and Disposition 2000, 28 5, 552-559.</ref>  identified various metabolites of Roxithromycin in human biological fluids. A total of 15 metabolites were found in bile, urine, and plasma by HPLC with ion trap mass spectrometric and electrochemical detection.
 ==References==