Pharmacokinetics of Oral Prednisone at Various Doses in Dogs: Preliminary Findings Using a Naïve Pooled-Data Approach

Abstract

This pilot study aimed to determine the plasma pharmacokinetics of prednisone and its active metabolite prednisolone following oral prednisone administration in dogs-using dosing regimens that cover anti-inflammatory to immuno-suppressive biological effects. Six healthy Beagle dogs were given 0.5, 1, 2, and 4 mg/kg prednisone orally once daily for 5 days, each successive course separated by a washout period of 9 days. At steady-state (Day 4), a sparse sampling design allowed for collection of blood from 2/6 individuals for each of the following time points: 0, 15, 30, 60, 90, 120, 240, 480, and 720 min. Prednisone and prednisolone were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral prednisone was rapidly converted to prednisolone in dogs (≤30 min), with plasma prednisolone reaching ∼6-fold greater levels (0-656.1 ng/mL) than prednisone (0-98.8 ng/mL) overall. The ratio of plasma prednisolone/prednisone was constant across the dosing regimens, indicating a non-saturation of the hepatic 11-β-hydroxysteroid dehydrogenase that converts the prodrug to the active metabolite in dogs. The level of both corticosteroids increased with increasing dosing regimens, albeit in a non-linear manner. Non-compartmental pharmacokinetic parameters are described, including peak concentration (C max), time of peak concentration (T max), area under the concentration-time curve (AUC last), and the elimination half-life (t 1/2) for both corticosteroids, as well as clearance and volume of distribution during the terminal phase (V z) for the administered drug (prednisone). In sum, the present study utilizes a sparse sampling and naïve pooled-data approach to estimate pharmacokinetic parameters for prednisone and prednisolone, providing supporting preliminary knowledge that can be used to optimize corticosteroid efficacy and minimize toxicity in canine patients.

Pharmacokinetics of Orally Administered Prednisolone in Alpacas

“…Due to the multiple downstream effects of prednisolone, there currently are not many recommendations regarding therapeutic concentrations of prednisolone in the veterinary literature. In beagles administered oral prednisolone at 2.0 mg/kg, maximum plasma concentrations of 58.2 ng/mL have been observed, this is similar to the maximum concentrations of 74 and 68 ng/mL observed in the alpacas in this study (35). This dosage in dogs has been described for the use as an anti-inflammatory agent as well as and antineoplastic agent (19,36).…”

Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs

“…Although plasma levels of ceftiofur were not evaluated in the present study, comparison with another group of dogs receiving the same dose of ceftiofur (5 mg/kg) ( 12 ) highlights two interesting findings: (1) Tear film concentrations reached ~ 9.3% of plasma levels (based on C max values), a value that is consistent with the tear-to-plasma ratio (12%) for another antibiotic recently tested in dogs (doxycycline); ( 4 ) and (2) time to reach maximal concentration was faster in tears than in plasma (2 h vs. 23.2 h, respectively). The latter finding was also described in dogs that were administered oral prednisone at a given dosage (0.5 mg/kg), ( 10 , 22 ) yet the potential explanation remains puzzling as one would expect T max to be consistently longer in tears when compared to the blood compartment, regardless of the drug or the dosage. This finding may be partly explained by the high variability in drug quantification inherent to tear fluid (i.e., disturbance of ocular surface homeostasis, depletion of tear fluid during tear sample collection), making calculations of T max less reliable than in plasma or other bodily fluids.…”

Prednisone Ameliorates Atrial Inflammation and Fibrosis in Atrial Tachypacing Dogs

“…49) To supplement the pharmacokinetics data provided by a pilot study, performing a full prednisone dose-response trial with a large sample size would be meaningful. 50)…”