The pharmacokinetics of transdermal flunixin meglumine in Holstein calves

Abstract

This study describes the pharmacokinetics of topical and intravenous (IV) flunixin meglumine in Holstein calves. Eight male Holsteins calves, aged 6 to 8 weeks, were administered flunixin at a dose of 2.2 mg/kg intravenously. Following a 10-day washout period, calves were dosed with flunixin at 3.33 mg/kg topically (transdermal). Blood samples were collected at predetermined times from 0 to 48 h for the intravenous portions and 0 to 72 h following topical dosing. Plasma drug concentrations were determined using liquid chromatography with mass spectroscopy. Pharmacokinetic analysis was completed using noncompartmental methods. The mean bioavailability of topical flunixin was calculated to be 48%. The mean AUC for flunixin was determined to be 13.9 h × ug/mL for IV administration and 10.1 h × ug/mL for topical administration. The mean half-life for topical flunixin was 6.42 h and 4.99 h for the intravenous route. The C following topical application of flunixin was 1.17 μg/mL. The time to maximum concentration was 2.14 h. Mean residence time (MRT) following IV injection was 4.38 h and 8.36 h after topical administration. In conclusion, flunixin when administered as a topical preparation is rapidly absorbed and has longer half-life compared to IV administration.

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows

“…The half‐life reported here (5.20 hr) is shorter in these cattle following multiple doses compared to those (6.42 hr) published following a single dose in younger Holstein calves (Kleinhenz et al., ). The time to maximum flunixin concentration ( T max ), maximum flunixin concentration ( C max ), and mean resident time (MRT) are similar to those in younger calves.…”

“…Flunixin has an oral bioavailability of 60% (Odensvik, ). The test product was shown to have true transdermal absorption in calves that were prevented from grooming following drug application (Kleinhenz et al., ). Furthermore, there are supporting data showing no difference between cattle allowed to groom and those not allowed to groom (US FDA (United States Food and Drug Administration), ).…”

Comparative plasma and interstitial fluid pharmacokinetics of flunixin meglumine and ceftiofur hydrochloride following individual and co‐administration in dairy cows

“…Plasma and ISF concentrations of FLU were determined using LC‐MS as previously described (Kleinhenz et al., ). The LOD was 3 ng/ml and the LOQ was 5 ng/ml.…”

Pharmacokinetics of transdermal flunixin in sows

“…Recently, a pour‐on formulation of flunixin for transdermal (TD) administration was approved for use in cattle in the European Union and United States (Finadyne Pour‐On, MSD Animal Health). Recent work on TD flunixin in calves demonstrated a longer half‐life and more rapid administration when compared to IV admin, suggesting TD administration may be a promising administration route in farm animals (Kleinhenz et al, ). However, the pharmacokinetic (PK) properties of flunixin administered TD in mature swine have not been evaluated.…”

“…Kleinhenz et al () reported a 48% F for TD flunixin in dairy calves (Kleinhenz et al, ). In mature swine, the mean F of FM was 76% and 22% for IM and oral routes, respectively (Pairis‐Garcia et al, ).…”