ABSTRACT
The pharmacokinetics and pharmacodynamics of meloxicam in piglets (16-23 days old) were studied using a stratified parallel group design. One group (n = 13) received 0.4 mg/kg meloxicam intravenously, while the other group (n = 12) received physiological saline solution. A carrageenan-sponge model of acute inflammation was used to evaluate the effects of meloxicam. The plasma clearance was low (0.061 L/kg/h), the volume of distribution was low (0.19 L/kg) and the elimination half-life was short (2.7 h). At most time points, the mean concentration of meloxicam in plasma exceeded the concentrations in exudate indicating a limited accumulation of the drug at the site of the inflammation. There were significant differences between the groups in the exudate prostaglandin E2 (PGE2) concentration, but the inhibition of PGE2 in the meloxicam group was limited. The inhibition of thromboxane B(2) (TXB2) production in serum in the meloxicam group was extensive, but of shorter duration than the PGE2 inhibition in exudate.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Thiazines/pharmacokinetics , Thiazoles/pharmacokinetics , Thromboxane A2/antagonists & inhibitors , Animals , Animals, Newborn , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Area Under Curve , Dinoprostone/antagonists & inhibitors , Female , Half-Life , Male , Meloxicam , Metabolic Clearance Rate , Swine , Thiazines/pharmacology , Thiazoles/pharmacology , Thromboxane A2/biosynthesisABSTRACT
Determination of plasma concentrations of pregnancy associated glycoproteins (PAG) has been used for early pregnancy diagnosis in cows. However, this is complicated by the presence of PAG in plasma for an extended period postpartum. The main objective of the present study was to investigate the postpartum elimination rates of pregnancy associated glycoproteins (PAG) in sheep, goats and cows in order to gain background information applicable to the use of PAG for pregnancy diagnosis in domestic ruminants. A second objective was to investigate whether PAG are transferred to the foetus and newborn, by measuring plasma PAG concentrations in calves, lambs and goat kids before and after colostrum feeding. PAG in the blood at parturition were eliminated by a first order process in the cows and ewes, while a two-step log-linear decline occurred in the goats. Estimated postpartum half-life of plasma PAG in the cows and ewes was 9 and 4.5 days, respectively. In the goats, half-lives were 3.6 and 7.5 days in the initial fast and terminal slow phase. Basal levels were reached 80-90 days postpartum in cows. Plasma PAG concentration can be used for pregnancy diagnosis from day 28 after AI, provided that the time interval from calving to AI is >60 days. Using a heterologous antibody RIA, we found 4 ng/mL to be the appropriate cut-off. Due to the presence of PAG residues from the previous gestation, the interval from AI to pregnancy diagnosis should increase by approximately 0.5 days beyond 28 days for each day of AI closer to calving than 60. Measurements in newborn ruminants suggested that PAG enter the foetal blood in utero and that colostral PAG are transferred to the newborn. Following the peak plasma concentration observed 1 day after birth in most of the animals, PAG were rapidly eliminated in a log-linear fashion.
