Enantiomeric disposition of ketorolac in goats following administration of a single intravenous and oral dose

Abstract

disposition of ketorolac in goats following administration of a single intravenous and oral dose. J. vet. Pharmacol. Therap. 32, 49-55.The purpose of this study was to investigate the stereospecific pharmacokinetics of ketorolac (KT) in goats following a single 2 mg ⁄ kg intravenous (i.v.) dose and a single 6 mg ⁄ kg oral dose. A stereoselective high pressure liquid chromatography assay was used to quantify ketorolac plasma concentrations. Pharmacokinetic parameters for both stereoisomers were estimated by model independent methods. Following an i.v. dose, the plasma concentration profiles for the stereoisomers were similar with half-lives of 1.05 ± 0.62 h for R-KT and 1.05 ± 0.61 h for S-KT. Clearance values for R-and S-KT after an i.v. dose were 0.53 ± 0.23 and 0.54 ± 0.23 LAEh ⁄ kg, respectively. Following an oral dose, the terminal half-lives were longer with values of 34.08 ± 11.81 and 33.97 ± 12.19 h for R-KT and S-KT, respectively. The average bioavailability was 133 ± 23% for R-KT and S-KT, respectively. The longer half-lives and high apparent bioavailability after oral dosing are suggestive of a slow absorption process in the gastrointestinal tract and recycling. The results indicate that interconversion of the stereoisomers of ketorolac is absent in goats. However, studies with individual isomers are needed before any conclusion can be drawn about the lack of bioinversion.(Paper

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs

“…). A similar profile was also observed in rats (Rivera‐Espinosa et al ., ) and in goats (Nagilla et al ., ). The reason of this increase in serum concentrations was not further investigated in our study, but on one hand could be attributed to an entero‐hepatic recycle of drug.…”

“…A wide range of analgesic drugs is used in dogs to control peri-and post-operative pain such as opioids, local anaesthetics, a 2 -agonist and nonsteroidal anti-inflammatory drugs (NSAIDs). The use of NSAIDs in veterinary medicine is very common especially for the treatment for musculoskeletal and abdominal pain (Nagilla et al, 2009), thanks to their activity on central sensitization in pathological pain besides peripheral activity in inflammatory status (Burian & Geisslinger, 2005). Ketorolac (KET), an heteroaryl acetic acid derivative, is an NSAID approved for use in humans that possesses potent analgesic activity (Sinha et al, 2009).…”

“…Due to these characteristics and the potent anti-inflammatory and analgesic activities, KET could represent a useful tool to control acute pain also in animals, such as in the post-operative period. However, the drug is not currently approved for the use in veterinary patients; thus, few pharmacokinetics and efficacy studies have been published in veterinary species (Mathews et al, 1996;Pasloske et al, 1999;Santos et al, 2001;Nagilla et al, 2007;Cagnardi et al, 2009;Nagilla et al, 2009). Data about pharmacokinetics correlated to clinical efficacy are relevant to propose a correct use of KET in veterinary species.…”

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

“…Adverse effects of KT are similar to those caused by other nonselective NSAIDs, but overall incidence in postoperative human patients is low (Elia, Lysakowski, & Tramer, ; Forrest et al., ; Reinhart, ). No veterinary study has specifically evaluated KT for safety, but no adverse effects have been reported after single dosing in calves, sheep, goats, dogs, cats or horses (Bianco et al., ; Ferraresi et al., ; Nagilla et al., , ; Pasloske et al., ; Santos et al., ; Semrad, ). Importantly, safety of repeated administration of KT in animals has not been evaluated.…”

A Simple and Sensisitive HPLC Method to Monitor Serum and Synovial Fluid Concentrations of Ketorolac in Reumathologic Patients

“…Though several chromatographic methods have been developed for the determination of KT by means of HPLC/UV or HPLC/mass spectrometry; some of these methods have a limit of quantification (LOQ) that is too high for evaluate permeation of KT in synovial fluid (Wang et al, 2001;Galan-Herera et al, 2008). Some are enantioselective (Nagilla et al, 2007;Nagilla et al, 2009) and require expensive chiral columns and length analysis times; some requires long time for treatment sample (Wu and Massey, 1990).…”