Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals

Womble, Ariel Y.; Giguère, Steeve; Lee, Elise A.; Vickroy, Thomas W.

doi:10.2460/ajvr.2001.62.1870

Cited by 78 publications

(98 citation statements)

References 35 publications

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“…In the present study, CLR was at least as active as ERY against R. equi in vitro, whereas AZI was eightfold less active. MIC 90 s of CLR and AZI against R. equi in the present study were considerably below achievable concentrations of these drugs in serum, pulmonary epithelial lining fluid, or bronchoalveolar cells following oral administration to foals (6,14,15). In contrast to the macrolides evaluated in the present study (ERY, CLR, and AZM), tilmicosin, a veterinary macrolide, has poor in vitro activity against R. equi, with MIC 90 s of Ͼ32 g/ml (4).…”

mentioning

confidence: 66%

“…In people, the incidence and the severity of side effects for these drugs are also considerably decreased from those for ERY (25). The pharmacokinetics of these antimicrobial agents in foals have recently been investigated (6,14,15). However, the paucity of in vitro susceptibility studies precludes the rational use of these antimicrobial agents for the treatment of R. equi infections in foals.…”

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confidence: 99%

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In Vitro Susceptibilities ofRhodococcus equiand Other Common Equine Pathogens to Azithromycin, Clarithromycin, and 20 Other Antimicrobials

Jacks¹,

Giguère²,

Nguyen

2003

Antimicrob Agents Chemother

109

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The objective of this study was to determine in vitro activities of azithromycin (AZM), clarithromycin (CLR), and 20 other antimicrobial agents against Rhodococcus equi and other common equine bacterial pathogens. A total of 201 bacterial isolates from various equine clinical samples were examined. CLR was more active than AZM against R. equi, with MICs at which 90% of the isolates were inhibited of 0.12 and 1.0 g/ml, respectively. Other antimicrobial agents highly active against at least 90% of R. equi isolates in vitro included rifampin, gentamicin, and imipenem. Both AZM and CLR showed good activity against beta-hemolytic streptococci and Staphylococcus spp. AZM was more active than other macrolides against Pasteurella spp. and Salmonella enterica.

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confidence: 66%

mentioning

confidence: 99%

In Vitro Susceptibilities ofRhodococcus equiand Other Common Equine Pathogens to Azithromycin, Clarithromycin, and 20 Other Antimicrobials

Jacks¹,

Giguère²,

Nguyen

2003

Antimicrob Agents Chemother

109

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“…Between-day accuracy was Ϫ3.6 to 9.1% of the nominal concentrations, and precision was 3.4 to 13.3% of mean control values. Drug concentrations in ELF were assessed through normalization to the concentration of urea in lavage fluid versus the concentration in plasma, and concentrations in BALCs were normalized to a mean macrophage cell volume of 1.2 l/10 6 cells in foals (Rennard et al, 1986;Jacks et al, 2001). Plasma concentrations of cholesterol and its metabolite 4␤-hydroxycholesterol (4␤OH-C) were assayed by using gas chromatography-mass spectrometry for an isotope-dilution method, with [26,26,26,27,27, H 6 ]4␤OH-C as an internal standard, as described previously (TomalikScharte et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Clarithromycin Is Absorbed by an Intestinal Uptake Mechanism That Is Sensitive to Major Inhibition by Rifampicin: Results of a Short-Term Drug Interaction Study in Foals

Peters¹,

Eggers²,

Oswald³

et al. 2012

Drug Metabolism and Disposition

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ABSTRACT:Pulmonary penetration of clarithromycin (CLR) in epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALCs) can be influenced by CYP3A4, by P-glycoprotein, and, according to our hypothesis, by a member of the organic anion-transporting protein (OATP) family, for which rifampicin (RIF) is inhibiting in single doses but inducing after long-term coadministration. To assess the partial inhibitory effect, we measured absorption and pulmonary distribution of CLR after short-term (2.5-day) coadministration of RIF, after which up-regulation is not expected. The drug interaction study was performed with five doses (12-h interval) of CLR (7.5 mg/kg) and RIF (10 mg/kg) in nine healthy foals; horse transporters are very similar in protein sequence and transcriptional regulation to the human analogs. RIF was equally distributed in ELF but reached half the plasma levels in BALCs. The deacetylated metabolite accumulated 1.4-to 6-fold in ELF and 8-to 60-fold in BALCs. CLR did not significantly influence the distribution of RIF. CLR and 14-hydroxyclarithromycin (14OH-CLR) accumulated approximately

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“…Between-day accuracy was Ϫ11.7 to 8.6% of the nominal concentrations and precision was 3.7 to 10.0% of the respective mean control values. CLR and 14-OH-CLR concentrations in ELF were assessed by normalizing to the concentration ratio of urea in plasma over bronchoalveolar fluid and in BALC to a mean macrophage cell volume of 1.2 l/10 6 cells in foals (Rennard et al, 1986;Jacks et al, 2001). Urea was quantified using a LT-UR 0010 kit (Labortechnick Eberhard Lehmann, Berlin, Germany).…”

Section: Methodsmentioning

confidence: 99%

Oral Absorption of Clarithromycin Is Nearly Abolished by Chronic Comedication of Rifampicin in Foals

Peters

Block²,

Oswald³

et al. 2011

Drug Metabolism and Disposition

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ABSTRACT:The delivery of clarithromycin (CRL) to its site of action in bronchial/alveolar epithelial cells (EC), bronchial epithelial lining fluid (ELF), and bronchoalveolar lavage cells (BALC) may be influenced by CYP3A4 and the drug transporters, ATP-binding cassette (ABC) B1 and ABCC2 and organic anion-transporting polypeptides (OATPs), which can be modulated and/or up-regulated via the nuclear pregnane X receptor (PXR) by rifampicin (RIF). Therefore, we evaluated the disposition and pulmonary distribution of CLR (7.5 mg/kg b.i.d., 21 days) and expression of ABCB1, ABCC2, OATP1A2, and OATP2B1 in EC and BALC before and after comedication of RIF (10 mg/kg b.i.d., 11 days) in nine healthy foals (41-61 days, 115-159 kg) in which the genetic homology of drug transporters is close to that of their human analogs. After RIF comedication, relative bioavailability of CLR decreased by more than 90%. Concentrations in plasma (29.8 ؎ 26.3 versus 462 ؎ 368 ng/ml), ELF (0.69 ؎ 0.66 versus 9.49 ؎ 6.12 g/ml), and BALC (10.2 ؎ 10.2 g/ml 264 ؎ 375 g/ml; all P < 0.05) were lowered drastically, whereas levels of the metabolite 14-hydroxyclarithromycin were not elevated despite higher 4␤-hydroxycholesterol/cholesterol plasma concentration ratio, a surrogate for CYP3A4 induction. In the presence of CLR, ABCC2 and PXR mRNA contents were significantly and coordinately (r 2 ‫؍‬ 0.664, P < 0.001) reduced in BALC after RIF. In EC, mRNA expression of OATP1A2 increased but that of OATP2B1 decreased (both P < 0.05). RIF interrupts oral absorption and decreases CRL plasma levels below the minimal inhibitory concentration for eradication of Rhodococcus equi. Evidence that RIF influences the cellular uptake of CLR in bronchial cells and the PXR expression in BALC in the presence of high CLR concentrations exists.

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Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals

Cited by 78 publications

References 35 publications

In Vitro Susceptibilities ofRhodococcus equiand Other Common Equine Pathogens to Azithromycin, Clarithromycin, and 20 Other Antimicrobials

In Vitro Susceptibilities ofRhodococcus equiand Other Common Equine Pathogens to Azithromycin, Clarithromycin, and 20 Other Antimicrobials

Clarithromycin Is Absorbed by an Intestinal Uptake Mechanism That Is Sensitive to Major Inhibition by Rifampicin: Results of a Short-Term Drug Interaction Study in Foals

Oral Absorption of Clarithromycin Is Nearly Abolished by Chronic Comedication of Rifampicin in Foals

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