Stereoselective pharmacokinetics of ketorolac in calves after a single intravenous and oral dose

Nagilla, Rakesh; Deshmukh, D. D.; Duran, Sue H.; Ravis, William R.

doi:10.1111/j.1365-2885.2007.00892.x

Cited by 14 publications

(26 citation statements)

References 24 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs

Cagnardi

Zonca

Gallo

et al. 2013

Vet Pharm & Therapeutics

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Ketorolac (KET) is a nonsteroidal anti‐inflammatory drug approved for the use in humans that possesses a potent analgesic activity, comparable to morphine, and could represent a useful tool to control acute pain also in animals. The clinical efficacy and pharmacokinetic profile of intravenous (IV) ketorolac tromethamine (0.5 mg/kg) were studied in 15 dogs undergoing gonadectomy. Intra‐operative cardiorespiratory variables were monitored, and post‐operative pain was assessed using a subjective pain score (0–24) in all dogs, whereas the pharmacokinetic profile of the drug was determined in 10 animals. During surgery, mean minimal alveolar concentration of isoflurane was 1.69 ± 0.11%, and normocapnia and spontaneous ventilation were maintained in all animals. During pain assessment, no significant differences between males and females were found, and in no case rescue analgesia was necessary. No adverse effects were reported. Serum samples were purified by solid‐phase extraction and analysed by HPLC with UV‐Vis detection. A large variability was observed in serum concentrations. The kinetics of ketorolac was described by a noncompartmental analysis. The elimination half‐life (t½λz) and ClB were 10.95 ± 7.06 h and 92.66 ± 84.49 mL/h/kg, respectively, and Vdss and Vz were 1030.09 ± 620.50 mL/kg and 1512.25 ± 799.13 mL/kg, respectively. AUC(0→last) and MRT(0→last) were 6.08 ± 3.28 h × μg/mL and 5.59 ± 2.12 h, respectively. The results indicate that ketorolac possess good post‐operative analgesic effects until about 6 h after administration in dogs undergoing moderately painful surgery.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs

Cagnardi

Zonca

Gallo

et al. 2013

Vet Pharm & Therapeutics

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Bianco

Moore

Cooper

et al. 2017

Vet Pharm & Therapeutics

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Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed.Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B 2 (TXB 2 ) and Prostaglandin E 2 (PGE 2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.

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“…Animal studies have shown that the antiinflammatory activity of Ketorolac resides in the (−) S entantiomer and that the (+) R entantiomer is pharmacologically inactive [7]. The pharmacokinetics of Ketorolac has been documented in humans [8][9][10][11][12][13][14][15] and animals including dogs [16], rats [17], calves [18], rabbits [19], goats [20], and sheep [21]. Objectives of this study was to determine the difference of tissue distribution of Ketorolac and its enantiomers in rats following a single oral dose of 3.2 mg/kg racemic mixture.…”

Section: Introduction ▼mentioning

confidence: 99%

Enantioselective Tissue Distribution of Ketorolac and its Enantiomers in Rats

2014

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The difference in tissue distribution of Ketorolac and its enantiomers were investigated in wistar rats. Separate high performance liquid chromatographic method was developed and validated for determination of Ketorolac and its enantiomers. Oyster BDS (150 × 4.6 mm id., 5 μm particle size) column was used for determination of concentration of Ketorolac. Ketorolac enantiomers were determined using Chiral-AGP column (100 × 4.0 mm I.D., particle size 5 μ, Chrom tech Ltd, Sweden). Detection was done at wavelength of 322 nm using an ultraviolet detector in the analytical system. Ketorolac enantiomers exhibit difference in their disposition in Wistar rats. In kidney, there was a significant difference in pharmacokinetic parameters. The Cmax was nearly 4 times and AUC 0-∞ was found to be more than double for S (-) Ketorolac than that of R (+) Ketorolac. MRT, Ke and t1/2 differ significantly in kidney. In liver, Cmax was found to be approximately 69% higher for S (-) Ketorolac compared to R (+) Ketorolac. AUC 0-∞ did not differ significantly for the enantiomers in liver. In liver, S (-) Ketorolac eliminated very fast in comparison to R (+) Ketorolac having t1/2 (one third) in comparison to R (+) Ketorolac. In lungs, there was no difference observed for Cmax and other parameters but AUC 0-∞ was found to be marginally higher for S (-) ketorolac.

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Stereoselective pharmacokinetics of ketorolac in calves after a single intravenous and oral dose

Cited by 14 publications

References 24 publications

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs

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

Enantioselective Tissue Distribution of Ketorolac and its Enantiomers in Rats

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