Prednisolone: what the FDA reviewed for dog products
2 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Prednisolone, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- PrednisTab® (NADA/ANADA 140-921)
PrednisTab® NADA 140-921, Original approval, November 08, 1991; sponsor Lloyd, Inc.; species: Dogs; foi_id 488; FDA PDF
Indication
Anti-inflammatory corticosteroid for collagen, dermal, allergic, ocular, otic and musculoskeletal conditions in dogs known to be responsive to anti-inflammatory corticosteroids.
Dose regimen
2.5 mg per 10 pounds body weight total daily dose (5-15 lb: 2.5 mg; 15-40 lb: 2.5 to 5 mg; 40-80 lb: 5 to 10 mg), Oral, Daily, given in divided doses 6 to 10 hours apart, 5.0 mg compressed tablets
The average total daily doses for dogs are as follows: 5 to 15 lb (2 to 7 kg) body weight 2.5 mg 15 to 40 lb (7 to 18 kg) body weight 2.5 to 5 mg 40 to 80 lb (18 to 36 kg) body weight 5 to 10 mg NOTES: The usual total daily dose of 2.5 mg per 10 pounds of body weight should be given in divided doses, 6 to 10 hours apart
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| bioavailability | 82±13 % (oral) | Human literature data (Ref.5) tabulated in the summary; row columns: availability (oral) %, urinary excretion %, bound in plasma %, clearance (mL/min kg), Vol. Dist. (liters/kg), half-life (hours) | Prednisolone 82±13 26±9 90-95 8.7±1.6 1.5±0.2 2.2±0.5 |
| other | 26±9 % urinary excretion | Human literature data (Ref.5) tabulated in the summary; row columns: availability (oral) %, urinary excretion %, bound in plasma %, clearance (mL/min kg), Vol. Dist. (liters/kg), half-life (hours) | Prednisolone 82±13 26±9 90-95 8.7±1.6 1.5±0.2 2.2±0.5 |
| protein binding | 90-95 % bound in plasma | Human literature data (Ref.5) tabulated in the summary; row columns: availability (oral) %, urinary excretion %, bound in plasma %, clearance (mL/min kg), Vol. Dist. (liters/kg), half-life (hours) | Prednisolone 82±13 26±9 90-95 8.7±1.6 1.5±0.2 2.2±0.5 |
| clearance | 8.7±1.6 mL/min kg | Human literature data (Ref.5) tabulated in the summary; row columns: availability (oral) %, urinary excretion %, bound in plasma %, clearance (mL/min kg), Vol. Dist. (liters/kg), half-life (hours) | Prednisolone 82±13 26±9 90-95 8.7±1.6 1.5±0.2 2.2±0.5 |
| other | 1.5±0.2 liters/kg volume of distribution | Human literature data (Ref.5) tabulated in the summary; row columns: availability (oral) %, urinary excretion %, bound in plasma %, clearance (mL/min kg), Vol. Dist. (liters/kg), half-life (hours) | Prednisolone 82±13 26±9 90-95 8.7±1.6 1.5±0.2 2.2±0.5 |
| half-life | 2.2±0.5 hours | Human literature data (Ref.5) tabulated in the summary; row columns: availability (oral) %, urinary excretion %, bound in plasma %, clearance (mL/min kg), Vol. Dist. (liters/kg), half-life (hours) | Prednisolone 82±13 26±9 90-95 8.7±1.6 1.5±0.2 2.2±0.5 |
| half-life | 200 min plasma half-life; 12-36 hr biologic half-life | Literature Table 1 (Relative Potencies of Corticosteroids, modified from Axelrod 1985); row columns: glucocorticoid potency, equivalent dose (mg), mineralocorticoid potency, plasma t1/2 (min), biologic t1/2 (hr) | Prednisolone 4 5 0 200 12-36 |
Target-animal safety
This information, bioequivalency data on pages 7 to 11 and additional clinical parameters measured pre and post- trial on page 10 support the thesis that absence of the 6alpha-methyl group on prednisolone has little effect on the relative safety of prednisolone in the dog.
| Finding | Quote |
|---|---|
| Clinical pathology (hematology, serum biochemistry, urinalysis) of the 19 bioequivalency-study dogs was within normal ranges before and after dosing | All of the clinical pathological parameters examined were within the range of normal accepted values prior to and after the dosing phase of the study. |
| Literature (Chastain & Graham 1979): prednisone at 0.22 mg/kg/day, 0.55 mg/kg/day or 1.1 mg/kg alternate days for 4 weeks caused adrenocortical atrophy/hypofunction; less severe with alternate-day dosing | Each course of prednisone administration resulted in adrenocortical atrophy and hypofunction, but adrenocortical suppression was less severe and slower in onset in the group given prednisone on alternate days. |
| Literature: skin atrophy and focal fatty change of the liver most evident at daily pharmacologic doses (0.55 mg/kg/day); none at replacement dose (0.22 mg/kg/day) | Extra-adrenal effects observed were atrophy of the skin and focal, fatty change of the liver. These changes were most evident in dogs given daily pharmacologic doses of prednisone (0.55 mg/kg/day). |
| Literature (Muller et al.): expected side effects of anti-inflammatory induction therapy are polydipsia, polyuria and polyphagia | Expected side effects with anti-inflammatory induction therapy include polydipsia, polyuria, and polyphagia. |
Effectiveness
Pipeline DESI approval: two-period crossover bioequivalency study of PrednisTab (prednisolone 5 mg tablets) vs the pioneer Medrol (methylprednisolone 1 mg tablets) in healthy adult mixed-breed dogs, single oral doses (5:4 mg ratio), 21-day washout; pharmacodynamic endpoints (circulating eosinophil suppression and blood glucose increase).; n = 9 female and 10 male (nineteen); primary endpoint: AUC, Cmin and Tmin of eosinophil counts; AUC, Cmax and Tmax of blood glucose (90% CI within 20% guideline); result: Bioequivalence shown for eosinophil AUC and Tmin and for glucose AUC and Cmax; eosinophil Cmin and glucose Tmax fell outside the 20% limit but were judged not biologically significant.
Nineteen healthy adult mixed-breed dogs (9 female and 10 male) obtained from Laboratory Animal Resources, Iowa State University were used.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Adverse reactions ascribed to treatment (bioequivalency study) | No adverse reactions that could be ascribed to treatments were noted in this study. |
Extraction notes: No margin-of-safety (dose multiple) study: the Target Animal Safety section is a literature review plus reference to the bioequivalency study's clinical pathology; TAS findings are therefore literature-derived and dose_multiples is empty. PK values are human literature data (Ref.5) tabulated in the summary, not canine data. Effectiveness rests on NAS/NRC DESI review of methylprednisolone plus pharmacodynamic bioequivalence.
PrednisTab® NADA 140-921, Supplemental approval, November 20, 1997; sponsor Lloyd, Inc.; species: Dogs; foi_id 1381; FDA PDF
Indication
See labeling (anti-inflammatory corticosteroid; indications per original NADA 140-921 approval).
Dose regimen
2.5 mg per 10 lb (4.5 kg) body weight per day (to 20 lb: 1.25 to 5 mg; 20 to 40 lb: 5 to 10 mg; 40 to 80 lb: 10 to 20 mg; 80 to 160 lb: 20 to 40 mg), Oral, Daily (average total daily oral dose), Supplement provides a new 20 mg tablet size
2.5 mg per 10 lb. (4.5 kg) body weight per day. Average total daily oral doses for dogs are as follows: to 20 lb. (2 to 9 kg) body weight........1.25 to 5 mg 20 to 40 lb. (9 to 18 kg) body weight..........5 to 10 mg 40 to 80 lb. (18 to 36 kg) body weight.......10 to 20 mg 80 to 160 lb. (36 to 73 kg) body weight......20 to 40 mg
Extraction notes: Category II supplemental approval adding a 20 mg tablet size; effectiveness and target animal safety refer to the original FOI for NADA 140-921 (November 8, 1991). No study data in this summary. Species stated only as 'non-food animal species (dogs)'.
Reproduce: foi_structured_search(query="Prednisolone") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).