Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies

Abstract

The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-time curve were common. Double peaks were also encountered when phenylbutazone was given to ponies deprived of food prior to, and allowed access to hay after, dosing. In this circumstance, mean times to peak concentration were much shorter (3.8 +/- 1.3 h after morning dosing and 5.3 +/- 1.5 h followed afternoon dosing). Absorption was more regular and double peaks were less apparent when food was withheld both before and after dosing. In order to explain these findings, it is tentatively postulated that, whereas some of the administered dose of phenylbutazone may be absorbed quickly, some may become adsorbed on to the feed and subsequently released by fermentative digestion in the large intestine and/or caecum. The consequences of delayed absorption in fed animals for toxicity and clinical efficacy, and for the use of phenylbutazone in equestrian sports, are considered. Delayed absorption in ponies given access to hay was not accompanied by a significant reduction in total absorption. Bioavailability was estimated to be approximately 69% in fed and 78% in unfed ponies. Estimates of bioavailability gave similar values for morning (72%) and afternoon (71%) dosing.

Pharmacokinetics of meloxicam in plasma and urine of horses

“…In contrast, for some NSAIDs that bind to cellulose, absorption is delayed for several hours and likely is in the distal segment of the digestive tract. 3 Meloxicam is intended for repeated administrations. The study reported here documented that with respect to F, there was no significant difference between the first and last oral administrations and that the data fit a bicompartmental model well, which is consistent with the hypothesis that meloxicam disposition (absorption, distribution, and elimination) is independent of time and dose.…”

“…5,r Feeding conditions of horses can influence the plasma concentration patterns of several NSAIDs. 3,11 Therefore, the influence of the feeding conditions on meloxicam disposition was investigated by use of 2 feeding regimens (fed and nonfed). The study reported here documented that the F for the oral route of administration was high for both regimens (85 ± 19% for nonfed horses and 96 ± 13% for fed horses) and not significantly different.…”

“…Administration of a drug after food has been withheld for a few hours leads to rapid absorption, whereas drug administration during or after a meal may result in sustained and erratic absorption. 3 Because efficacy of meloxicam is related to the achieved plasma concentration, the first objective of the study reported here was to determine F of meloxicam in horses for the oral route of administration and qualify the influence of feeding conditions (fed vs not fed) on the rate and extent of meloxicam absorption.…”

Right dorsal colitis in the horse: minireview and reports on three cases in Ireland

“…NSAIDs can cause ulceration throughout the entire gastrointestinal tract of horses [10,13,6]. The exact reason for the localization of ulceration in the right dorsal colon has not been elucidated; however, one hypothesis is that phenylbutazone is bound extensively to roughage and is released after fermentation in the large colon [14]. There is prolonged contact time between the drug and the right dorsal colon due to the slow transit time and the narrowing of the lumen at the junction of the right dorsal colon and the transverse colon [3].…”

Oral dosage regimen in the nonlinear pharmacokinetics of sulphadimethoxine in pigs

“…Absorption rate constant, Tmax and apparent elimination rate constant after intraduodenal administration of 20 mg/kg of SDM in pigs. It is well known that the pharmacokinetics after oral administration is unpredictable, especially in practical field conditions, because of fluctuations in the absorption process due to the prandial state and differences in individual gastrointestinal tracts (3,4,6,7,13). The fluctuation of the time course of Cf, possibly due to the change in ka during the experimental period, was also observed in those animals (numbers 2 and 3) which had a relatively small ka value (Figure 2).…”