Pharmacokinetics and disposition of clenbuterol in the horse

Soma, Lawrence R.; Uboh, Cornelius E.; Guan, Fuyu; Moate, Peter J.; Luo, Yang; Teleis, D.; Li, R.; Birks, Eric K.; Rudy, Jeffrey A.; Tsang, Deborah S.

doi:10.1111/j.1365-2885.2004.00553.x

Cited by 21 publications

(11 citation statements)

References 26 publications

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“…The LOQ restricted quantification of CLB in plasma beyond 96 h, but not in urine. A mono‐exponential decline was described in plasma and bi‐exponential decay in urine (Soma et al. , 2004).…”

Section: Discussionmentioning

confidence: 99%

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Tissue distribution of clenbuterol in the horse

Soma¹,

Uboh²,

Guan³

et al. 2004

Vet Pharm & Therapeutics

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Plasma and tissue concentrations of clenbuterol (CLB) were determined following oral (p.o.) administration of 1.6 microg/kg twice daily (b.i.d.) for 2 weeks. Horses were administered the last dose on morning of day 15, killed at 0.25, 24, 48, and 72 h post-administration. At 0.25 h, the highest tissue concentrations of CLB were found in the liver (16.21 ng/g), lung (6.48 ng/g), left ventricle (4.99 ng/g), kidney (3.35 ng/g), bronchi (2.56 ng/g), right ventricle (2.08 ng/g), and eye fluids (1.09 ng/g) all of which were higher than that of plasma (1.10 ng/mL). The elimination half-lives (t(1/2k)) for CLB in tissues ranged from 21.2 to 56.3 h, the longest were in the eye fluids (56.9 h), spleen (21.2 h), cerebrum (27.1 h), cerebellum (21.5) and cecum (23.7 h). The t(1/2k) for plasma was 10.9 h. Tissue/plasma ratios of liver (14.7), lung (5.9), left ventricle (4.6), kidney (3.1), bronchi, (2.3) and right ventricle (1.9) were high at 0.25 h and remained elevated up to 72 h. Accumulation and sustained high concentration of CLB relative to plasma in these tissues contributed to the prolonged elimination and the ability to quantify CLB in plasma and urine for a prolonged period.

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Section: Discussionmentioning

confidence: 99%

“…No metabolites have been described or identified in the horse (Guan et al. , 2002; Soma et al. , 2004).…”

Section: Discussionmentioning

confidence: 99%

Tissue distribution of clenbuterol in the horse

Soma¹,

Uboh²,

Guan³

et al. 2004

Vet Pharm & Therapeutics

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“…The pharmacokinetics, tissue distribution and metabolism of clenbuterol have been studied in a number of species, including human . Residual clenbuterol in meat and muscle tissue is also a matter of concern in the food industry and in connection with drug abuse .…”

Section: Introductionmentioning

confidence: 99%

Enantioselective disposition of clenbuterol in rats

Hirosawa

Ishikawa

Ogino

et al. 2013

Biopharm & Drug Disp

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Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. Here, we examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats.Concentrations of clenbuterol enantiomers in plasma, urine, and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity, and precision, and clenbuterol enantiomers in 0.1-mL volumes of plasma were precisely quantified at concentrations as low as 0.25 ng/mL. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2 mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17 L/kg) was significantly higher than that of (+)-S-clenbuterol (4.14 L/kg). Total body clearance of (-)-R-clenbuterol (13.5 mL/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5 mL/min/kg). An in-situ absorption study in jejunal loops showed no difference in residual amount between the (-)-R-and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R-and (+)-S-clenbuterol in rat plasma were 48.8, and 33.1%, respectively. These results indicated that there are differences in distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding.

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“…The LLOQ for plasma and urine was 50 and 200 pg/mL, respectively. In previous pharmacokinetic studies for β 2 ‐adrenoceptor agonists in horses, the LLOQ of clenbuterol was 130 pg/mL in plasma and 500 pg/mL in urine (Soma et al ., ), and the LLOQ of terbutaline was 150 pg/mL in plasma (Törneke et al ., ). The analytical sensitivity of PCR in this study was inferior to that found in a human study, which was 10 pg/mL for plasma (Kobayashi et al ., ), but the sensitivity in the current study was sufficient to conduct pharmacokinetic analyses of PCR in horses.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetics of β 2 ‐adrenoreceptor agonists in horses were studied for clenbuterol (Soma et al ., ) and terbutaline (Törneke et al ., ). The CL and

t_{1 false/ 2 λ_{2}}

of PCR in this study were four times higher (0.12 L/h/kg) and three times shorter (9.2 h) than those of clenbuterol, respectively, and four times lower (1.9 L/h/kg) and three times longer (1.2 h) than those of terbutaline, respectively.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of procaterol in thoroughbred horses

Kusano

Nomura

Toju

et al. 2015

Vet Pharm & Therapeutics

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Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.

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Pharmacokinetics and disposition of clenbuterol in the horse

Cited by 21 publications

References 26 publications

Tissue distribution of clenbuterol in the horse

Tissue distribution of clenbuterol in the horse

Enantioselective disposition of clenbuterol in rats

Pharmacokinetics of procaterol in thoroughbred horses

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