Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs

Abstract

To determine the plasma pharmacokinetics of suppository acetaminophen (APAP) in healthy dogs and clinically ill dogs. This prospective study used six healthy client-owned and 20 clinically ill hospitalized dogs. The healthy dogs were randomized by coin flip to receive APAP orally or as a suppository in crossover study design. Blood samples were collected up to 10 hr after APAP dosing. The hospitalized dogs were administered APAP as a suppository, and blood collected at 2 and 6 hr after dosing. Plasma samples were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry. In healthy dogs, oral APAP maximal concentration (C =2.69 μg/ml) was reached quickly (T =1.04 hr) and eliminated rapidly (T1/2 = 1.81 hr). Suppository APAP was rapidly, but variably absorbed (C =0.52 μg/ml T =0.67 hr) and eliminated (T = 3.21 hr). The relative (to oral) fraction of the suppository dose absorbed was 30% (range <1%-67%). In hospitalized ill dogs, the suppository APAP mean plasma concentration at 2 hr and 6 hr was 1.317 μg/ml and 0.283 μg/ml. Nonlinear mixed-effects modeling did not identify significant covariates affecting variability and was similar to noncompartmental results. Results supported that oral and suppository acetaminophen in healthy and clinical dogs did not reach or sustain concentrations associated with efficacy. Further studies performed on different doses are needed.

Effects of housing environment on oral absorption of acetaminophen in healthy Beagles

“…The pharmacokinetics of acetaminophen following oral administration in the present study were different from those published previously [23][24][25][26] (Table 2). Our study used Beagles, whereas previous studies used mixed-breed dogs, Greyhounds, or Labrador Retrievers, which could account for the differences noted, especially in that other studies 27,28 have identified pharmacologic and metabolic differences among dog breeds.…”

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

“…A population PK analysis with nonlinear mixed effects (NLME) modeling approach using established methods was performed to fit the serum fluconazole concentration data to a compartmental PK model using commercial software Phoenix NLME TM (version 8.0, Certara USA, Inc.) similar to previous studies (Mould & Upton, 2012; Muñana et al., 2018; Papich, 2017; Sikina, Bach, Lin, Gehring, & KuKanich, 2018).…”

Paracetamol: A Focus on Dogs

“…A study in which APAP was administered rectally showed that it had a much lower bioavailability than orally administered APAP (Sikina et al, 2018). Although it was rapidly absorbed and eliminated, at a dose of 9.5-14 mg/kg, it was unlikely to achieve therapeutic concentrations.…”