A comparison of the pharmacokinetics and tissue penetration of spiramycin and erythromycin

Kavi, J.; Webberley, J. M.; Andrews, J. M.; Wise, R.

doi:10.1093/jac/22.supplement_b.105

Cited by 16 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 This conversion is especially efficient at low pH such as in stomachs of the patients treated with this antibiotic. 35 This conversion also occurs in the environment as well as during the sample preparation and analysis and, therefore, most of the methods for determination of ERY in environmental samples include ERY-H 2 O rather than parent ERY. 13,[19][20][21]34 In addition to ERY-H 2 O, the present study included ERY-EE, which was shown to be TP formed during biodegradation, 22 as well as DM-ERY, which can be either metabolite formed by demethylation in the liver 36 or microbial TP.…”

Section: Methodsmentioning

confidence: 99%

Occurrence and Behavior of Macrolide Antibiotics in Municipal Wastewater Treatment: Possible Importance of Metabolites, Synthesis Byproducts, and Transformation Products

Senta

Kostanjevečki

Krizman-Matasic

et al. 2019

Environ. Sci. Technol.

View full text Add to dashboard Cite

A one-year study on the occurrence and fate of macrolide antibiotics and their metabolites, synthesis by-products and transformation products (TPs) was performed in the wastewater treatment plant of the city of Zagreb (Croatia). The target compounds were found in all analyzed influent and effluent samples, with the total concentrations of azithromycin-, clarithromycin-and erythromycin-related compounds reaching up to 25, 12 and 0.25 μg/L, respectively. The most prominent individual constituents were the parent macrolides azithromycin and clarithromycin. However, a substantial contribution of their derivatives, formed by deglycolysation and microbial phosphorylation, was also detected. In addition, widespread presence of several linearized non-target TPs was confirmed for the first time in real wastewater samples by suspect screening analysis. Complex characterization of macrolide-derived compounds enabled decoupling of industrial and therapeutic sources from the insitu transformations. Due to the high inputs, incomplete removal and/or formation of several TPs during the conventional wastewater treatment, the average mass load of azithromycin-related compounds in secondary effluents exceeded 3.0 g/day/1000 inhabitants. This is the first study to reveal the importance of metabolites, by-products and TPs for the overall mass balance of macrolide antibiotics in urban wastewater systems.

show abstract

Section: Methodsmentioning

confidence: 99%

Occurrence and Behavior of Macrolide Antibiotics in Municipal Wastewater Treatment: Possible Importance of Metabolites, Synthesis Byproducts, and Transformation Products

Senta

Kostanjevečki

Krizman-Matasic

et al. 2019

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…Spiramycin’s pharmacokinetic properties are governed by physicochemical properties and likely not by aldehyde reactivity. Multiple reports on human PK properties have been published with this class of drugs, and typical oral dosing regimens are 2.5 g BID or up to 1 g TID. Pediatric dosage is at 25 mg/kg.…”

Section: Antibacterialsmentioning

confidence: 99%

Curse or Cure? A Perspective on the Developability of Aldehydes as Active Pharmaceutical Ingredients

Gampe¹,

Verma²

2020

J. Med. Chem.

View full text Add to dashboard Cite

There is a dichotomy between the increasing utility of aldehydes as tool molecules that bind to “undruggable” protein sites and the designation of the aldehyde functional group as a structural alert by the medicinal chemistry community. Herein we compile information about pharmacologically active aldehydes that are being used in humans. We summarize the learnings from these data, discuss advantages and challenges associated with aldehydes, and derive strategies for the successful development of aldehydes within drug discovery programs.

show abstract

“…The apparent half-life varies with the dose and ranges from 2 to 6 h for clarithromycin and from 2 to 9 h for its 14-(R)-hydroxyclarithromycin metabolite after the administration of doses of 100 to 1,200 mg given orally. The elimination half-life of erythromycin is approximately 1 to 6 h after oral administration of a 500-mg dose (26).…”

mentioning

confidence: 99%

Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin

Conte

Golden

Duncan

et al. 1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The intrapulmonary pharmacokinetics of orally administered clarithromycin (500 mg every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were studied in 32 healthy adult volunteers. Four of the subjects, two in the clarithromycin group and two in the erythromycin group, were smokers. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed at 4, 8, 12, 24, and 48 h after administration of the last dose of clarithromycin and at 4, 8, and 12 h after administration of the last dose of erythromycin. Clarithromycin was measured by high-performance liquid chromatography, and erythromycin was measured by a microbiological assay. No systemic sedation was used. There were no major adverse events. The concentrations of antibiotics in epithelial lining fluid (ELF) were calculated by the urea dilution method. The volumes (mean ؎ standard deviation) of ELF were 1.9 ؎ 2.0 ml and 1.5 ؎ 0.7 ml in the clarithromycin and erythromycin groups, respectively (P > 0.05). There was no effect of smoking on the amount of bronchoalveolar lavage fluid recovered, the volume of ELF, or the number of erythrocytes present in the lavage fluid (P > 0.05 for all comparisons). The total number of alveolar cells, however, was almost threefold greater in the smokers versus that in the nonsmokers (P < 0.05). Clarithromycin was concentrated in ELF (range, 72.1 ؎ 73.0 g/ml at 8 h to 11.9 ؎ 3.6 g/ml at 24 h) and alveolar cells (range, 505.8 ؎ 293.1 g/ml at 4 h to 17.0 ؎ 34.0 g/ml at 48 h). 14-(R)-Hydroxyclarithromycin was also present in these compartments, but at lower concentrations than the parent compound. The concentrations of erythromycin in ELF and alveolar cells were low at 4, 8, and 12 h following the last dose of drug (range, 0 to 0.8 ؎ 0.1 g/ml in ELF and 0 to 0.8 ؎ 1.3 g/ml in alveolar cells). The clinical significance of any antibiotic concentrations in these compartments is unclear. The data suggest, and we conclude, that clarithromycin may be a useful drug in the treatment of pulmonary infections, particularly those caused by intracellular organisms.Clarithromycin is a semisynthetic macrolide antibiotic that contains a 14-member lactone ring (32). It is active against Streptococcus pneumoniae, Haemophilus influenzae group A streptococci, Staphylococcus aureus, Staphylococcus epidermidis, Moraxella catarrhalis, Chlamydia pneumoniae, Mycobacterium pneumoniae, Toxoplasma gondii, Listeria monocytogenes, legionellae, atypical mycobacteria, and Mycobacterium leprae (2,7,19,22,23,25,28,31,38,42). Like other macrolides, clarithromycin is concentrated in phagocytic cells (5,6,9,30), and it is active against intracellularly growing bacteria (1, 15, 36).The kinetics of clarithromycin are nonlinear (11,13,16). The apparent half-life varies with the dose and ranges from 2 to 6 h for clarithromycin and from 2 to 9 h for its 14-(R)-hydroxyclarithromycin metabolite after the administration of doses of 100 to 1,200 mg given orally. The elimination half-life of erythromycin is approximately 1 to 6 h after oral administrat...

show abstract

A comparison of the pharmacokinetics and tissue penetration of spiramycin and erythromycin

Cited by 16 publications

References 0 publications

Occurrence and Behavior of Macrolide Antibiotics in Municipal Wastewater Treatment: Possible Importance of Metabolites, Synthesis Byproducts, and Transformation Products

Occurrence and Behavior of Macrolide Antibiotics in Municipal Wastewater Treatment: Possible Importance of Metabolites, Synthesis Byproducts, and Transformation Products

Curse or Cure? A Perspective on the Developability of Aldehydes as Active Pharmaceutical Ingredients

Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin

Contact Info

Product

Resources

About