High performance liquid chromatography and pharmacokinetics of the non‐steroidal anti‐inflammatory drug oxindanac in calves

Abstract

A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.375 to 62.5 micrograms/ml were 90.2-107.8% with interassay coefficients of variation of 2.1-22.3%. The limit of detection was estimated as 0.10 micrograms/ml and the limit of quantification calculated to be 0.24 micrograms/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t1/2 was long (t1/2 21.2 h after i.v. injection) and absorption was rapid (t1/2a 0.072 h) and complete (F > 100%) following i.m. administration. Bioavailability was incomplete (F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed two absorption phases (t1/2's 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB2 production, with mean Emax values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.o. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36-48 h.

Characteristics of Acetaminophen Absorption in Healthy Unweaned Calves as an Indirect Measurement of the Oroduodenal Transit Rate of Liquid Meals

“…The flat absorption curves in calves fed by RT may indicate, that only minimal amounts of AP if any are absorbed via the ruminal wall, but that absorption occurs in the intestine after a decent and delayed transport from the ruminoreticulum to the duodenum. Other authors described a biphasic pattern of serum concentrations in the absorption of another non‐opiate analgesic when given orally to calves (King et al., 1994) and sheep (Cooke and Nicholson, 1981). Cooke presumed that the first peak occurred after a quick direct passage through the abomasum, whereas the second peak stands for a delayed transit of a fraction of the test‐meal after a short retention in the ruminoreticulum.…”

Correlation between the pharmacokinetics of oxindanac and inhibition of serum thromboxane B2in calves

“…x g at 4°C for 20 min and the plasma stored at -70°C before it was analysed for total oxindanac concentration by HPLC (King et al, 1994a). The limits of detection and quantification were 0.10 and 0.24 pg/ml, respectively.…”

“…This dilution allowed TxB, concentrations in the range 5-300 ng/ml to be assayed in one run. Standard curves were prepared in 'stripped serum' as previously described (King et al, 1994a). There was no interference between oxindanac and the RIA.…”

“…Pharmacokinetic parameters were calculated for individual calves using formulae previously described (King et al, 1994a) and the symbols proposed by Aronson et al (1988). Values for slopes and intercepts are given as means (k SEM) as they were derived by least squares regression and should therefore be normally distributed (Powers, 1990).…”