Pharmacokinetics of azithromycin after single oral dosing of experimental animals

d'Avila, Domingos O.; Kolacny-Babic, Lidija; Plavsić, F

doi:10.1002/bdd.2510120704

Cited by 27 publications

(19 citation statements)

References 10 publications

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“…Ramsey and colleagues have suggested the importance of determining fetal tissue AZ concentrations to assist in determining whether AZ should be recommended for use in treating perinatal infections (45). Davila and colleagues reported that tissue (including lung and liver) AZ concentrations were higher than serum concentrations in both rabbits and rats following oral dosing (49). Work by Girard et al suggests that AZ is effective against localized infections by Gram-positive and Gram-negative bacteria in rodent models even when serum AZ concentrations are below the MIC (50).…”

Section: Discussionmentioning

confidence: 99%

“…Similar values have been reported by other investigators. For example, Escudero and colleagues (48) cited work by Davila et al (49), noting that "tissue/ serum ratios in liver, kidney, lung and ileum of 1381, 1171, 1261 and 1682, respectively, have been reported in rats after a single (200 mg/kg) oral administration of azithromycin." Similarly, Foulds and colleagues have reported that AZ concentrations in tissues commonly range from 10 to 100 times the serum AZ concentrations (51).…”

Section: Discussionmentioning

confidence: 99%

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Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

Kemp

Miura

Payne

et al. 2014

Antimicrob Agents Chemother

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g Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-daygestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

Kemp

Miura

Payne

et al. 2014

Antimicrob Agents Chemother

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“…While objective and subjective impairments were similar after midazolam alone and in combination with azithromycin, a clear increase was recorded after eryhtromycin + midazolam, both in psychomotor impairment and in plasma midazolam concentrations. This qualitative difference between azithromycin and erythromycin is not likely to be due to differences in their hepatic concentrations, since the level of azithromycin in the liver is large, at least in animals [11]. Azithromycin has a large volume of distribution [4], it is widely distributed into tissues, mainly excreted unchanged in bile, and is partly metabolised in the liver as well.…”

Section: Discussionmentioning

confidence: 99%

Azithromycin does not alter the effects of oral midazolam on human performance

Mattila

Vanakoski

Idänpään-Heikkilä

1994

Eur J Clin Pharmacol

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Since macrolide antibiotics inhibit the oxidative hepatic metabolism of various drugs, including midazolam, the present double blind studies were conducted to find out if azithromycin, a new macrolide of the azalide type, would inhibit the metabolism of midazolam and enhance the effects of midazolam on human performance. In Study I, 64 healthy medical students, divided in four parallel groups received placebo, midazolam (10 mg or 15 mg), and midazolam 10 mg combined with azithromycin (500 mg + 250 mg). In Study II, three males received oral midazolam 10 mg in combination with placebo, azithromycin or erythromycin 750 mg (as a positive control) in a cross-over trial. Objective and subjective tests were done before the intake of midazolam and 30 and 90 min after it, and venous blood was sampled for the assay of midazolam. In the placebo group in Study I, the mean numbers of letters cancelled (LC) at baseline, 30 min and 90 min were 21, 20 and 20, respectively, and the corresponding mean numbers of correct digit symbol substitutions (DSS) were 126, 137 and 140, indicating a practice effect. Midazolam 10 mg impaired these performances (21, 13 and 12 for LC, and 127, 113 and 111 for DSS). Either dose of midazolam produced clumsiness, mental slowness and poor subjective performance, midazolam 15 mg being slightly more active. The corresponding, scores in the azithromycin+midazolam group were 21, 16, 16 for LC, and 132, 121 and 119 for DSS, the only significant difference from placebo being the impairment of DSS at 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Species differences in pharmacokinetic parameters and drug metabolism for numerous pharmaceutics have been well documented in domestic and exotic animal species. 3,4,9,15,20 Therefore, clinical pharmacology of therapeutic agents in avian species is an area of research that is needed to insure proper dosing and treatment.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Azithromycin in the Blue and Gold Macaw (Ara Ararauna) After Intravenous and Oral Administration

Carpenter¹,

Olsen²,

Randle-Port³

et al. 2005

Journal of Zoo and Wildlife Medicine

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Azithromycin is classified as an azalide, a subclass of macrolide antimicrobials with a broad spectrum of activity in vitro against many potential bacterial pathogens including spirochetes, anaerobes, and Chlamydia trachomatis. Because of limited data on the use of azithromycin in avian medicine, this study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen in clinical practice. Azithromycin (10 mg/kg) was administered via crop lavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr post-azithromycin administration. Following a 4-wk washout period, the study was repeated with a complete crossover study performed. Concentration of azithromycin in plasma samples was quantified using a validated liquid chromatography/mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Based on the pharmacokinetic data generated from this study, a starting dose of azithromycin at 10 mg/kg p.o. every 48 hr for susceptible bacterial infections in blue and gold macaws is recommended.

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Pharmacokinetics of azithromycin after single oral dosing of experimental animals

Cited by 27 publications

References 10 publications

Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

Azithromycin does not alter the effects of oral midazolam on human performance

Pharmacokinetics of Azithromycin in the Blue and Gold Macaw (Ara Ararauna) After Intravenous and Oral Administration

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