Comparative pharmacokinetics of minocycline in foals and adult horses

Abstract

The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6- to 9-week-old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells. After i.v. administration to foals, minocycline had a mean (±SD) elimination half-life of 8.5 ± 2.1 h, a systemic clearance of 113.3 ± 26.1 mL/h/kg, and an apparent volume of distribution of 1.24 ± 0.19 L/kg. Pharmacokinetic variables determined after i.v. administration to adult horses were not significantly different from those determined in foals. Bioavailability was significantly higher in foals (57.8 ± 19.3%) than in adult horses (32.0 ± 18.0%). Minocycline concentrations in PELF were higher than in other body fluids. Oral minocycline dosed at 4 mg/kg every 12 h might be adequate for the treatment of susceptible bacterial infections in foals.

The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity

“…Alternately, had plasma concentrations been obtained, the variability may be more clearly defined as due to GI and liver absorption. Previous studies investigating the difference between intravenous and oral administration have shown reduced bioavailability when the drug is given orally in adult horses versus foals . Furthermore, despite identical dosing and ad libitum feeding regimes, the concentrations in Giguere et al .…”

“…Furthermore, despite identical dosing and ad libitum feeding regimes, the concentrations in Giguere et al . were higher than that reported in Schnabel et al . The reason for this discrepancy was concluded to be unknown.…”

“…Throughout the seal study period, tear doxycycline concentrations were approximately 10% of plasma concentrations, but a significant correlation between plasma and tear doxycycline concentrations was not concluded. While the exact percentage of plasma concentrations is not known for the equine tear studies, extrapolations can be drawn from previous studies with similar dosages . Our study corroborates evidence that minocycline has a moderate plasma protein binding level, which may contribute to its high levels in tears.…”

Effect of feeding on the pharmacokinetics of oral minocycline in healthy adult horses

“…While significant differences in T max were not identified between oral‐fasted and oral‐fed groups, the T max of 5 hr in oral‐fed versus 2 hr in oral‐fasted horses suggests that hay might delay drug absorption. In contrast to fasted bioavailability (38.6%), oral‐fed bioavailability (15.7%) was much lower than previously reported for minocycline in adult horses (Echeverria et al., ; Giguère et al., ; Schnabel et al., ). Previous minocycline studies reported intragastric administration with various feeding protocols: ad libitum grass hay with pelleted feed twice daily (Schnabel et al., ); ad libitum grass hay (Giguère et al., ); or two flakes of grass hay twice daily (Echeverria et al., ).…”

“…In contrast to fasted bioavailability (38.6%), oral-fed bioavailability (15.7%) was much lower than previously reported for minocycline in adult horses (Echeverria et T A B L E 2 Plasma pharmacokinetic variables (mean ± SD unless otherwise specified) after IV (2.2 mg/kg) or oral (4.0 mg/kg) administration of minocycline to six adult horses. Horses treated orally were either fasted overnight and fed hay 2 hr after drug administration (fasted) or fed hay prior to drug administration (fed) 2016; Giguère et al, 2016;Schnabel et al, 2012). Previous minocycline studies reported intragastric administration with various feeding protocols: ad libitum grass hay with pelleted feed twice daily (Schnabel et al, 2012); ad libitum grass hay ; or two flakes of grass hay twice daily (Echeverria et al, 2016).…”