Effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following intravenous and transdermal administration to Holstein calves.

OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves. ANIMALS 8 healthy weaned Holstein bull calves. PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression. RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration. CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.

Immediate and long term effects of endurance and high intensity interval exercise on linear and nonlinear heart rate variability.

OBJECTIVES: Recovery of cardiac autonomic modulation following exercise can be measured using heart rate variability. The objective of this study was to investigate and compare recovery of autonomic cardiac regulation over three days following a single session of high intensity interval training compared to endurance training. DESIGN: Nine untrained students completed two exercise protocols in a one-way crossover design. The endurance protocol consisted of 45min of moderate intensity cycling, and the high intensity interval protocol of six 30s sets of high intensity cycling. METHODS: Cardiac autonomic activity recovery was measured over three days post-exercise for two hours immediately following each exercise session and each morning thereafter using linear and nonlinear heart rate variability analysis. RESULTS: Both linear and nonlinear measures were significantly decreased immediately following exercise indicating loss of vagal activity. Root mean sum of squared differences (p=0.031) and high frequency (p=0.031) were suppressed following the interval exercise only. The long term correlation of the heart rate applying detrended fluctuation analysis was decreased immediately following endurance training (p=0.039) and trended to increase immediately following the interval protocol (p=0.156). Sample entropy was decreased immediately following both the endurance (p=0.023) and interval (p=0.031) protocols. No exercise effects were noted from 24h post exercise onwards. CONCLUSIONS: High intensity interval training had a greater impact on neurocardiac activity than moderate intensity endurance training as indicated by both linear and nonlinear heart rate variability measures.

Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

OBJECTIVE: This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. DESIGN: Cohort study with repeated-measures design. METHODS: Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1ß, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. RESULTS: ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03). CONCLUSION: This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.