Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone

Abstract

This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08-0.25) h, respectively. Median (range) elimination half-lives for IA and IM administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3-compartment model was fitted to the plasma dexamethasone concentration-time curve following the IV administration of DSP; alpha, beta, and gamma half-lives were 0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following the PO administration, the median absorption and elimination half-lives were 0.34 (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1-3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.

Pilot study to quantify the time to clear dexamethasone from plasma and urine of adult horses following a single nebulisation

“…11,14,15 Depending on the dose rate, clearance from plasma after intravenous and intramuscular administration has been reported as 48-72 h, 9,12,13 whereas clearance in plasma after intra-articular administration was complete in 5/6 horses by 72 h. 13 There was one horse in the present study that had a plasma concentration of dexamethasone of 0 at 32 h but then registered a reading of 0.1 ng/mL at 96 h. This was unexpected and may have been associated with redistribution of the drug into fat or muscle tissue after nebulisation before being released back into the circulation. Current regulatory recommendations for horses in competition, subjected to blood and/or urine samples, are based on the intravenous, intramuscular or intra-articular administration of a single dose of dexamethasone.…”

Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in pigs

“…However, in horses a faster t max of 0.16 h was recently observed (Soma et al, 2013). After an IM injection, DEX sodium phosphate is fully bioavailable in pigs (F = 131%), horses (F = 100%; Soma et al, 2013) and broiler chickens (F = 123%; Watteyn et al, 2013). In dogs, an IM administration of DEX alcohol resulted in a relatively early C max at 0.63 h and a complete absorption, while in cattle a delayed C max at 4.27 h and an absolute bioavailability of only 67% was observed.…”

“…However, in horses a faster t max of 0.16 h was recently observed (Soma et al, 2013). After an IM injection, DEX sodium phosphate is fully bioavailable in pigs (F = 131%), horses (F = 100%; Soma et al, 2013) and broiler chickens (F = 123%; Watteyn et al, 2013).…”

“…Conversely, in dogs, cattle, horses and humans, a clearance of <0.6 L/ h kg was reported (Toutain et al, 1982(Toutain et al, , 1983Rohdewald et al, 1987;Greco et al, 1993;Hochhaus et al, 2001;Soma et al, 2013). In most species, the V d of DEX is <2 L/kg (Toutain et al, 1982(Toutain et al, , 1983Hochhaus et al, 2001;Soma et al, 2013).…”

Poly-beta-amino-esters nano-vehicles based drug delivery system for cartilage

“…The half-life of drugs in joint is about few hours,9, 43 thus “wash out” from cartilage is known to reduce treatment efficacy. For this reason it is important that a new delivery system for cartilage not only improves uptake but also retention7, 9; we have shown that DEX could be retained in cartilage through the use of PBAE-DEX for longer periods of time than when a commercial DEX phosphate solution is used (Figure 4).…”