Background Acetaminophen is utilized in human infants for pain management and fever. Neonatal foals might benefit from administration of acetaminophen but effective and safe dosage regimens for neonatal foals remains to be determined. Objective The objective was to determine the plasma pharmacokinetics of acetaminophen following oral administration of a single dose of 20 mg/kg or 40 mg/kg to neonatal foals. A secondary objective was to evaluate any changes in hematology and biochemistry profiles. Study design Randomized study. Methods Eight clinically healthy 7–9-day old Quarter Horse foals (3 colts and 5 fillies) received a single oral dose of acetaminophen either 20 (n = 4) or 40 (n = 4) mg/kg. Hematology and biochemistry profiles were evaluated before and 7 days after drug administration. Blood samples were collected before and 8 times after acetaminophen administration for 48 h to quantify plasma acetaminophen concentrations. Plasma pharmacokinetic parameters were estimated using non- compartmental analysis. Results The median peak plasma concentrations (and range) occurred at 1.5 (0.5–2) hours, and 1.0 (1–2) hours for the 20 and 40 mg/kg doses. The maximum plasma concentration (and range) was 12 (7.9–17.4) μg/mL for the 20 mg/kg dose and 14 (11–18) μg/mL for 40 mg/kg dose. The median AUC0-∞ ranged from 46 to 100 and 79 to 160 h*-μg/mL for the 20 and 40 mg/kg dose, respectively. Hematology and biochemistry profiles remained within normal limits. Conclusion Plasma disposition of acetaminophen after oral administration of 20 and 40 mg/kg to neonates is comparable to adult horses. However, safety and the optimal dosage regimen of acetaminophen for treating pain and or pyrexia in neonates in this age group remains to be determined.

/pdf/pharmacokinetics-of-acetaminophen-after-a-single-oral-3a7wwa4f.pdf

Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7–9 Day-old foals

The pharmacokinetic profile of paracetamol in koalas is described when administered orally at 15 mg/kg; followed by the same dose, administered every 12 hours (hrs), repeated five times. After the initial oral administration, the median (range) maximal plasma concentration (Cmax), the time Cmax was reached (Tmax) and elimination half-life (t1/2) were 16.93 μg/mL (13.66 to 20.25 μg/mL); 4 hrs (4 to 8 hrs) and 5.54 hrs (4.66 to 7.67 hrs), respectively. When paracetamol was administered orally at 15 mg/mL every 12 hrs, the trough total plasma concentration range remained comparable to the therapeutic range in humans i.e. 4 to 20 μg/mL that is known to provide some analgesia. However, there is a smaller proportion of free drug (i.e. not bound to plasma proteins; and the active form) available in koala plasma (approximately 40% unbound) compared to human plasma (approximately 80% unbound). Consequently, even when there are similar total drug plasma concentrations in both koala and human plasma, the therapeutic efficacy may be reduced in koalas compared to humans. The initial oral dose and subsequent twice daily doses resulted in no obvious adverse effects in any koala. Haematology, plasma electrolyte and biochemical analyte values remained within their reference ranges eight hrs after the last dose but there was a significant change in alanine transaminase (ALT) levels (an increase), and in total protein (a decrease) (both p = 0.03). A dose of 15 mg/kg was also administered as a subcutaneous injection, diluted 50:50 with saline, to two koalas. As the oral formulation and the subcutaneous administration resulted in comparable absorption, the study focused on the oral profile. Based on these results there is an argument to recommend a slight increase in the oral paracetamol dose for the koala, however further investigation is required to confirm whether repeated administration of a slightly higher dose may be associated with more severe or additional significant changes in haematology, electrolytes or biochemical analytes. However, a preferable recommendation would be to administer this dosage of paracetamol in combination with another analgesic such as tramadol, as a subcutaneous injection, to improve efficacy.

Pharmacokinetic profile of oral and subcutaneous administration of paracetamol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy

Lors d’une suspicion de fracture phalangienne chez le cheval, la qualité de la sédation-analgésie est essentielle pour assurer la sécurité des intervenants, le confort de l’animal, et permettre l’évaluation clinique ainsi que la stabilisation du membre avant tout transport. Cet article propose une approche raisonnée du choix des molécules sédatives et analgésiques disponibles chez le cheval, en tenant compte de leur potentiel thérapeutique, de leurs effets indésirables et des considérations légales. Le transport ne doit être envisagé qu’après contrôle de la douleur et une immobilisation adéquate du membre atteint. Les alpha-2-agonistes sont les sédatifs de choix, à associer à des opioïdes pour l’analgésie et une synergie des effets sédatifs. L’administration d’anti-inflammatoires non-stéroïdiens (AINS) est recommandée si le cheval est hémodynamiquement stable. Des adjuvants comme la kétamine ou l’acépromazine peuvent compléter le protocole selon les besoins. À domicile, l’analgésie à long terme doit être individualisée. Elle repose principalement sur les AINS, dont le choix et le suivi visent à éviter les effets indésirables et à optimiser l’analgésie. Des recommandations pratiques de surveillance lors d’administration prolongée d’AINS sont proposées. Certains adjuvants peuvent également être ajoutés à domicile. Cette démarche vise à améliorer la prise en charge globale des chevaux traités de manière conservatrice pour une fracture de phalange. 

Sédation et analgésie du cheval pour l’immobilisation avant transport et prise en charge à domicile lors d’une fracture de phalange

Simple Summary Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in equine practice for a variety of painful or inflammatory conditions. This review discusses the clinical pharmacology of NSAIDs in adult horses and methods of evaluating the therapeutic effect of these drugs in equine research. Abstract This review firstly examines the underlying pathophysiology of pain and inflammation associated with orthopedic disease and endotoxemia. Then, it reviews the clinical pharmacology (pharmacokinetics and pharmacodynamics) of both conventional and non-conventional NSAIDs in the adult horse, and finally provides an overview of different modalities to evaluate the therapeutic efficacy of NSAIDs in research.

https://www.mdpi.com/2076-2615/13/10/1597/pdf?version=1683704770

The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses

BACKGROUND
Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness.


OBJECTIVES
To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness.


STUDY DESIGN
Longitudinal.


METHODS
Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC-MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated by body-mounted inertial sensor (BMIS) and 10-point subjective lameness score on day 21 and compared to untreated baseline evaluation on day 35. Clinicopathological analysis (n = 12), hepatic biopsy (n = 6) and gastroscopy (n = 6) were evaluated on days -1 and 22.


RESULTS
Maximum plasma acetaminophen concentration (Cmax ) was 20.83 ± 10.25 μg/mL at time (Tmax ) 0.40 ± 0.22 h on day 7. The Cmax on day 21 was 17.33 ± 6.91 μg/mL with a Tmax of 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post-treatment; Significant percent improvement was detected in PDmax for horses with hindlimb lameness at 1, 2 and 8 h post-treatment. There were no significant differences in gastroscopy or hepatic biopsy scores between days -1 and 22.


MAIN LIMITATIONS
Small sample size, multi-limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation.


CONCLUSIONS
In horses with naturally occurring chronic lameness, acetaminophen at 30 mg/kg produced a transient improvement in subjective lameness and BMIS evaluation. Acetaminophen may not be effective as a monotherapy. Acetaminophen was safe following 21 days of 30 mg/kg PO every 12 h, with no evidence of clinically significant changes in clinicopathological analysis, hepatic biopsy or gastric ulceration scores.

Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.

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Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.