Some Pharmacokinetic Parameters of R-(–)- and S-(+)-Ketoprofen: The Influence of Age and Differing Physiological Status in Dairy Cattle

Abstract

The pharmacokinetic parameters of ketoprofen have previously been studied in cattle, but no studies have been performed on differing ages and metabolic situations in these animals. The aim of this work was to study the possible modifictions of the pharmacokinetics of ketoprofen enantiomers that may result from age, lactation or gestation in dairy cattle. Three groups of Holando Argentino cattle contained, respectively, 8 cows in early lactation, 8 pregnant cows and 8 newborn calves. Four animals from each group received the enantiomer R-(-)-ketoprofen, the other four animals received the S-(+) enantiomer, all by intravenous injection at a dose of 0.5 mg/kg. Significant differences between the three categories of animals were obtained in elimination half-life (t1/2) (1.52, 0.87 and 0.31 and 1.71, 0.69 and 0.26 in newborn calves, cows in early lactation and cows in gestation, respectively), mean residence time (MRT) (0.45, 1.25, 2.20 and 0.38, 0.99, 2.47 h, in cows in gestation, cows in early lactation and newborn calves, respectively) and area under the plasma concentration-time curve (AUC) (0.87, 2.93, 3.24, and 0.67, 2.78, 5.13 (microg/h)/ml in cows in gestation, cows in early lactation and newborn calves, respectively, for the R-(-) and S-(+) enantiomer, respectively. In calves, there was a significant difference in AUC (3.24 vs 5.13 (microg/h)/ml between R-(-)- and S-(+)-ketoprofen. In view of the differences between calves and adult cattle in the pharmacokinetic results for ketoprofen, the effects of age and physiological status (lactation, gestation) should be taken into account for therapeutic regimens.

Pharmacokinetic Parameters of (R)-(−) and (S)-(+)-Flurbiprofen in Dairy Bovines

“…Further studies are warranted to clarify the metabolism or flurbiprofen and to determine the extent and possibility of stereoselectivity in biliary excretion of the newborn calves. An enantiomeric difference related to age has been found previously following administration of (R)-(−)-and (S)-(+)-ketoprofen; the half life in calves was longer than in cows (Igarza et al, 2004). These results indicate the metabolic differences in the same species between these compounds of similar chemical structure.…”

Area/Moment and Compartmental Modeling of Pharmacokinetics During Pregnancy: Applications to Maternal/Fetal Exposures to Corticosteroids in Sheep and Rats

“…Most papers published on the pharmacokinetics of drugs in pregnancy report clearance and volume parameters calculated using either traditional mammillary compartmental or non-compartmental methods (1)(2)(3). Other pharmacokinetic papers provide descriptive parameters such as area under the curve, half-life, terminal rate constants, concentration maximum (Cmax), time to reach Cmax, and mean residence time (4)(5).…”

Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age

“…, 2004). Igarza et al. (2004) showed that newborn calves had lower clearance and longer elimination half‐life of ketoprofen compared to adult cows.…”