Multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine in the cat

Abstract

The purpose of this study was to evaluate the multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine alone and in combination in cats. Seven healthy cats were included in this randomized-crossover study. The cats were assigned to groups designated to receive cimetidine alone (15 mg/kg, p.o., q12 h), piroxicam alone (0.3 mg/kg, p.o., q24 h), and piroxicam combined with cimetidine (both at aforementioned doses). The cats were dosed for 10 days followed by at least a 2-week washout period between trials. Serial blood samples were collected following the first and last doses and analyzed utilizing a high-performance liquid chromatography with mass spectrometry detection (LC/MS) assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Endoscopic evaluation of the gastric mucosa was performed and serum urea nitrogen (SUN), creatinine, alkaline phosphatase (ALP), and alanine transaminase (ALT) activities were evaluated. There were not a clinically relevant difference between the pharmacokinetic parameters of piroxicam administered alone or in combination with cimetidine after either the first or last dose. Gastric ulcers were not observed in any cats although gastric erosions were. The SUN, creatinine, ALP, and ALT activities remained within reference ranges for all cats. It appears that once daily, short-term use of piroxicam alone and in combination with cimetidine in cats is relatively safe based on the parameters evaluated in this study. However, further studies are necessary to determine the long-term gastrointestinal safety of piroxicam.

Clinical signs, treatments, and outcome in cats with transitional cell carcinoma of the urinary bladder: 20 cases (1990–2004)

“…12 However, none of the cats in our study received that drug combination. 22 The drug is generally well tolerated in dogs but can cause clinically relevant gastric ulceration; renal and hepatic toxicoses may also develop. Single-agent treatment with piroxicam has been used in many dogs with TCC of the urinary bladder; reported median survival associated with that regimen is 181 days.…”

Nonsteroidal anti-inflammatory drugs in cats: a review

“…2003). Multiple‐dose pharmacokinetics and acute safety have been evaluated for piroxicam administered at 0.3 mg kg −1 daily for 10 days, with and without concurrent cimetidine administration (Heeb et al. 2005).…”

“…The mean half‐life increased from 11 hours on day 1 to 14 hours on day 10. Cimetidine reduced the half‐life of piroxicam, but not significantly (Heeb et al. 2005).…”

“…Four of seven cats receiving piroxicam developed mild to severe gastric erosions; however, they remained clinically asymptomatic. Two of seven cats receiving both piroxicam and cimetidine (15 mg kg −1 PO every 12 hours) developed mild erosions (Heeb et al. 2005).…”

Evaluation of adverse events in cats receiving long-term piroxicam therapy for various neoplasms

“…Single and multi-dose pharmacokinetics of piroxicam has been established in the cat. Heeb et al 10,12 found that 0.3 mg/kg appeared well tolerated as a single oral or intravenous dose, and also when dosed orally for 10 consecutive days. There is very little published information on the clinical use of piroxicam in cats and the effective dose is unknown.…”