Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep

Cárceles, C. M.; Font, Albert; Escudero, Elisa; Espuny, A; Marı́n, Pedro; Fernández-Varón, Emilio

doi:10.1111/j.1365-2885.2005.00680.x

Cited by 12 publications

(9 citation statements)

References 29 publications

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“…administration was 4.502 ± 1.487 h; this is somewhat longer than the half‐lives recorded in non‐lactating (1.41 h) and lactating goats (3.32 h) (Ambros et al., 2007). In contrast, the present finding was quite a bit shorter than that recorded for azithromycin both in sheep, 47 h (Carceles et al., 2005a), and goats, 32 h (Cárceles et al., 2005b). In their studies, the prolonged half‐life is attributed to a slow, rate‐limiting release of azithromycin from tissue into plasma, accompanied by excretion and metabolism (Carceles et al., 2005a).…”

Section: Discussioncontrasting

confidence: 99%

Pharmacokinetics and Mammary Residual Depletion of Erythromycin in Healthy Lactating Ewes

Goudah

Shah

Shin

et al. 2007

Journal of Veterinary Medicine Series A

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The aim of this investigation was to examine the pharmacokinetics and mammary excretion of erythromycin administered to lactating ewes (n = 6) by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes at a dosage of 10 mg/kg. Blood and milk samples were collected at pre-determined times, and a microbiological assay method was used to measure erythromycin concentrations in serum and milk. The concentration-time data were analysed by compartmental and non-compartmental kinetic methods. The serum concentration-time data of erythromycin were fit to a two-compartment model after i.v. administration and a one-compartment model with first-order absorption after i.m. and s.c. administration. The elimination half-life (t(1/2beta)) was 4.502 +/- 1.487 h after i.v. administration, 4.874 +/- 0.296 h after i.m. administration and 6.536 +/- 0.151 h after s.c. administration. The clearance value (Cl tot) after i.v. dosing was 1.292 +/- 0.121 l/h/kg. After i.m. and s.c. administration, observed peak erthyromycin concentrations (Cmax) of 0.918 +/- 0.092 microg/ml and 0.787 +/- 0.010 microg/ml were achieved at 0.75 and 1.0 h (Tmax) respectively. The bioavailability obtained after i.m. and s.c. administration was 91.178 +/- 10.232% and 104.573 +/- 9.028% respectively. Erythromycin penetration from blood to milk was quick for all the routes of administration, and the high AUC milk/AUC serum (1.186, 1.057 and 1.108) and Cmax-milk/Cmax-serum ratios reached following i.v., i.m. and s.c. administration, respectively, indicated an extensive penetration of erythromycin into the milk.

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Section: Discussioncontrasting

confidence: 99%

Pharmacokinetics and Mammary Residual Depletion of Erythromycin in Healthy Lactating Ewes

Goudah

Shah

Shin

et al. 2007

Journal of Veterinary Medicine Series A

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“…The essential characteristics of macrolide antibiotics are the presence of high tissue concentrations in tissues and significant accumulation in phagocytic cells that remained for a long time after plasma concentrations declined to low levels. That is even more apparent in the azalide sub-class as azithromycin, gamithromycin, or tulathromycin [16][17][18][19]. High tissue concentrations per se are not usually thought to be relevant to efficacy, especially for extracellular organisms.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Tildipirosin in Ewes after Intravenous, Intramuscular and Subcutaneous Administration

Galecio¹,

Escudero²,

Cerón³

et al. 2020

Animals

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A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 ± 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t½λz) was 17.16 ± 2.25, 23.90 ± 6.99 and 43.19 ± 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 ± 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (>70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.

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“…As such, a number of investigators have assessed the pharmacokinetics of AZ in gravid (29,41) and nongravid (34,(42)(43)(44) animal models, as well as in humans (14,45,46). Although the MP pharmacokinetics of AZ in humans at term (45) and in the late second trimester (46) are well described, there remains a lack of data describing the fetal uptake of AZ in the second trimester of pregnancy.…”

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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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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Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep

Cited by 12 publications

References 29 publications

Pharmacokinetics and Mammary Residual Depletion of Erythromycin in Healthy Lactating Ewes

Pharmacokinetics and Mammary Residual Depletion of Erythromycin in Healthy Lactating Ewes

Pharmacokinetics of Tildipirosin in Ewes after Intravenous, Intramuscular and Subcutaneous Administration

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

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