Clenbuterol plasma concentrations after repeated oral administration and its effects on cardio‐respiratory and blood lactate responses to exercise in healthy Standardbred horses

Abstract

To evaluate the effects of clenbuterol on cardio-respiratory parameters and blood lactate relation to exercise tolerance, experimental horses performed standardized exercise tests on a high-speed treadmill before and after administration of the drug. Clenbuterol was administered in feed to six healthy Standardbreds at a dose rate of 0.8 micrograms/kg b.wt twice daily for 5.5 days. Each horse was tested twice, without and with a respiratory mask, during two consecutive days. One week elapsed between the baseline tests without drug and the tests with clenbuterol treatment (each horse served as its own control). The results show an unchanged heart rate response to exercise 2 h after the last clenbuterol administration. The blood lactate response and the arterial oxygen tension during exercise did not differ before and after drug treatment. The oxygen uptake as well as pulmonary ventilation relative to the work load performed was essentially unaffected. The arterial pH during exercise was significantly increased (P less than 0.05) following clenbuterol treatment. Plasma levels of clenbuterol were maximal 2 h post-administration with values between 0.45 and 0.75 ng/ml. The plasma half-life of elimination was 10.4 h (+/- 2.25 SD). In conclusion, clenbuterol did not cause any major effects on the cardio-respiratory and blood lactate parameters studied in healthy horses performing submaximal exercise tolerance tests.

Detection, pharmacokinetics and cardiac effects following administration of clenbuterol to exercised horses

“…Following cessation of administration, the half-life of elimination of clenbuterol in the present study was 10.4 ± 4.4 h. This is in agreement with the half-life calculated in previous studies (10.4 [9] and 7 h [11]). Clenbuterol fell below detectable levels in plasma by 2-7 days post administration of the final dose in all horses studied for the low-dose regimen.…”

“…Clenbuterol fell below detectable levels in plasma by 2–7 days post administration of the final dose in all horses studied for the low‐dose regimen. This is similar to previous reports whereby clenbuterol was nondetectable in plasma by 72 h , 96 h and 7 days following administration of the final dose. Soma and colleagues reported that the drug was below the LOQ (13 pg/ml) in 3 of 6 horses studied by 96 h post administration (the final time point investigated) and nondetectable in the other 3.…”

“…In the study reported here, clenbuterol was well absorbed following oral administration, reaching a mean maximal plasma concentration of 473 ± 231 pg/ml at 1.42 ± 2.62 h. Absorption (time to Tmax) was slightly more rapid, although not significantly different, following administration of the last dose (1.07 ± 1.36 h) compared with the first, but the extent of absorption was equivalent between the 2 doses. These findings are comparable with a previous study [9] whereby a dose of 0.8 μg/kg bwt of clenbuterol granules administered b.i.d. for a total of 5.5 days resulted in maximal plasma concentrations of 450-750 pg/ml at 2 h post administration.…”

Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs

“…but the ECso-values using isotonic recordings were much higher than in our present study. In this study, using isometric recordings, the observed ECso-value for clenbuterol shows very good agreement with the therapeutic plasma levels reported earlier (Kallings et al, 1991). and guinea-pigs (1.9 x lo-* M) (Martin et aZ., 1994).…”

Intratracheal clenbuterol in the horse: its pharmacological efficacy and analytical detection

“…clenbuterol had no untoward effects on the circulatory system of exercising horses. Kallings et al (1991) found that oral clenbuterol did not cause any major effects on cardio‐respiratory and blood lactate variables in healthy horses performing submaximal exercise. Slocombe et al (1992) found that i.v.…”