Studies of meclofenamic acid and two metabolites in horses‐pharmacokinetics and effects on exercise tolerance

Abstract

The pharmacokinetics and the effects on treadmill exercise of the anti-inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non-compartmental analysis showed a mean absorption time of 4.3 h. The pharmacokinetics of two metabolites of meclofenamic acid were also studied in two of the horses. The elimination half-lives of the two metabolites were virtually the same in each horse (3.0 h and 3.4 h). The blood lactate response to exercise was significantly decreased after treatment with meclofenamic acid, indicating a lower utilization of the glycolytic ('anaerobic') energy contribution during exercise. Circulatory capacity was apparently unaffected with an unchanged heart rate response to exercise.

Few Drugs Display Flip-Flop Pharmacokinetics and These Are Primarily Associated with Classes 3 and 4 of the BDDCS

“…It appears here that dissolution of this poorly soluble drug yielded the flip‐flop kinetics for the suspension, with disintegration of the capsule (or dissolution of unwetted particles) causing a further increase in the terminal half‐life. As noted in Table , an additional BDDCS Class 2 drug, meclofenamic acid, was found to exhibit flip‐flop kinetics in horses . As with the great majority of the drugs in Table , meclofenamic acid exhibits a rapid i.v.…”

“…Notably, nedocromil has an inherently longer elimination half‐life (13.8 h) than any of the other drugs (0.3–7.7 h) that displayed convincing flip‐flop kinetics. Two BDDCS Class 2 drugs and one Class 1 drug are reported to exhibit flip‐flop pharmacokinetics.…”

“…As noted in Table 1, an additional BDDCS Class 2 drug, meclofenamic acid, was found to exhibit flip-flop kinetics in horses. 37,38 As with the great majority of the drugs in Table 1, meclofenamic acid exhibits a rapid i.v. half-life, 1.4 h. Meclofenamic acid would not be expected to exhibit flip-flop kinetics in humans because the package insert indicates that following oral dosing in 10 subjects the mean elimination half-life was 1.3 h, ranging from 0.8 to 2.1 h.…”

Pharmacokinetics of sodium meclofenamate in pre-ruminant cattle

“…The pharmacokinetics of sodium meclofenamate after intravenous and intramuscular administration to calves, as well as those reported in several animals species, have been best described using a two -compartment open models (Aitken and Sandford, 1975;Encinas et al, 1995;Johansson et al, 1991).…”

Spurious urine excretion drug profile in the horse due to bedding contamination and drug recycling: the case of meclofenamic acid

“…Hence for i.v. application, meclofenamic acid (Sigma, Saint Quentin Fallavier, France) was dissolved at a concentration of 10% in a mixture of PEG 400/water (25/75, v/v solution, as described by Johansson et al. , 1986, 1991).…”