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Pharmacokinetics of Meloxicam Following Intramuscular, Subcutaneous, and Oral Administration in White Storks (Ciconia ciconia)

This study characterizes the pharmacokinetics of meloxicam in white storks, finding that while subcutaneous administration offers a practical alternative to intramuscular injection with comparable systemic exposure, oral administration results in significantly lower and more variable bioavailability.

Original authors: Yigit Gunes, Ebuderda Gunay, Nurcin Yilmaz, Emine Irem Deveci, Dilek Ozturk Civelek, Ceren Anlas, Tulay Bakirel, Oya Ustuner, Ali Serhan Coskun, Duygu Sultan Oran, Alper Okyar

Published 2026-07-02

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Yigit Gunes, Ebuderda Gunay, Nurcin Yilmaz, Emine Irem Deveci, Dilek Ozturk Civelek, Ceren Anlas, Tulay Bakirel, Oya Ustuner, Ali Serhan Coskun, Duygu Sultan Oran, Alper Okyar

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

The Big Picture: A "Drug Test" for Storks

Imagine you are a wildlife doctor trying to help an injured White Stork. You want to give it a painkiller called Meloxicam to help it feel better. But here's the problem: birds are very different from each other. A medicine that works perfectly for a pigeon might be useless for a stork, or even dangerous.

This study was like a "drug test" to figure out exactly how White Storks handle this specific painkiller. The researchers wanted to know: Does it matter how we give the medicine? (Shooting it into a muscle, injecting it under the skin, or giving it as a pill?)

The Experiment: The "Three-Route" Race

The researchers took six White Storks (three males, three females) that were already being cared for at a rehabilitation center because they couldn't be released back into the wild.

They treated each bird three times, with a long break in between each time to make sure the previous medicine was completely gone. In each round, they gave the exact same dose (1 mg per kg of body weight) but used a different delivery method:

Intramuscular (IM): Like a shot deep into the chest muscle.
Subcutaneous (SC): Like a shot just under the skin (over the breastbone).
Oral (PO): Like giving a pill or liquid by mouth.

They then took small blood samples over 24 hours to see how much medicine was in the bird's bloodstream at every step.

The Results: Who Wins the Race?

Think of the medicine as a runner trying to get from the starting line (where it was given) to the finish line (the bloodstream where it does its work).

1. The Muscle Shot (IM): The Sprinter

What happened: This was the fastest route. The medicine jumped into the bloodstream almost immediately.
The Peak: The amount of medicine in the blood reached its highest point very quickly (in about 40 minutes) and was very high.
The Analogy: This is like sprinting straight to the finish line. You get there fast, and you have a lot of energy right away.

2. The Skin Shot (SC): The Marathon Runner

What happened: This was a bit slower. The medicine had to travel through the tissue under the skin before hitting the bloodstream.
The Peak: It took about 2 hours to reach the top, and the peak wasn't quite as high as the muscle shot.
The Total Distance: However, over the full 24 hours, the total amount of medicine the bird got was almost exactly the same as the muscle shot.
The Analogy: This is like a marathon runner. They start slower and take a winding path, but they cover the same total distance as the sprinter by the end of the day.

3. The Pill (PO): The Stalled Car

What happened: This route was a disaster for getting the medicine into the blood.
The Peak: The highest level of medicine was tiny—about 7 times lower than the muscle shot.
The Total Distance: Over 24 hours, the bird only absorbed about 15% of the medicine compared to the shots. The other 85% was lost (likely digested or filtered out before it could help).
The Analogy: Imagine trying to drive a car to the finish line, but the car keeps stalling, losing fuel, and getting stuck in traffic. You barely make any progress compared to the runners.

Key Takeaways from the Study

Birds are unique: You cannot guess how a stork handles medicine just by looking at other birds. This study showed that storks handle this drug differently than vultures or parrots.
Skin vs. Muscle: Giving the shot under the skin (SC) is just as effective as giving it in the muscle (IM) for White Storks. This is great news for vets because shots under the skin are often easier and less painful for the bird than deep muscle shots.
Pills are risky: Giving Meloxicam as a pill to a White Stork is not a good idea if you want it to work well. The bird's body seems to block most of it from entering the blood.
Time matters: The medicine stayed in the bird's system for a long time (about 10 to 19 hours depending on how it was given), meaning it doesn't disappear quickly.

What the Researchers Did NOT Say

It is important to stick to what the paper actually found:

They did not say exactly what the "perfect" dose should be for a sick stork. They only tested one specific dose.
They did not prove that the medicine cured the pain; they only measured how the drug moved through the blood.
They did not test this on baby storks or storks that are very sick; they only tested healthy, stable birds.

The Bottom Line

If you are a vet treating a White Stork and need to give Meloxicam, don't use a pill. Use a shot. And if you have to choose between a muscle shot and a skin shot, the skin shot is a perfectly fine (and perhaps gentler) alternative that gets the same amount of medicine into the bird's system.

Technical Summary: Pharmacokinetics of Meloxicam in White Storks

Problem Statement
Meloxicam (MLX) is a preferential cyclooxygenase-2 (COX-2) inhibitor widely utilized in avian medicine for managing pain and inflammation, particularly in wildlife rehabilitation. However, significant interspecific variability in drug disposition among avian taxa limits the reliability of empirical dose extrapolation. While MLX has been studied in raptors, psittacines, and domestic poultry, no pharmacokinetic data existed for the white stork (Ciconia ciconia). This species, frequently admitted to rehabilitation centers for traumatic and infectious conditions, currently lacks species-specific dosing guidelines, forcing clinicians to rely on data from phylogenetically distant birds, which increases the risk of therapeutic failure or adverse drug reactions.

Methodology
The study employed a randomized, three-way crossover design involving six clinically stable, non-releasable white storks (three males, three females; 1–3 years old; mean weight 3.03 ± 0.30 kg). Each bird received a single 1 mg/kg dose of MLX via three distinct routes: intramuscular (IM), subcutaneous (SC), and oral (PO). Treatments were separated by a two-week washout period, calculated to exceed 10 elimination half-lives based on prior avian data to prevent carry-over effects.

Blood samples were collected at 0, 5, 15, 30 minutes, and 1, 2, 4, 6, 8, 10, 12, and 24 hours post-administration. Plasma MLX concentrations were quantified using a validated High-Performance Liquid Chromatography (HPLC) method with diode-array detection (HPLC-DAD), utilizing piroxicam as an internal standard. The analytical method demonstrated linearity from 0.05 to 50 µg/mL with a lower limit of quantification (LLOQ) of 0.05 µg/mL. Pharmacokinetic parameters were determined using non-compartmental analysis.

Key Results
The study revealed marked differences in MLX pharmacokinetics depending on the administration route:

Absorption and Peak Concentration ( $C_{max}$ ): IM administration resulted in the most rapid absorption, reaching a $C_{max}$ of 11.49 ± 2.34 µg/mL at a median $t_{max}$ of 0.67 hours. SC administration produced a lower $C_{max}$ (6.43 ± 1.62 µg/mL) at a later $t_{max}$ (2.00 hours). PO administration yielded the lowest and most variable exposure, with a $C_{max}$ of 1.53 ± 0.89 µg/mL and a $t_{max}$ of 4.00 hours. All pairwise comparisons for $C_{max}$ were statistically significant ( $p < 0.05$ ).
Systemic Exposure (AUC): Systemic exposure ( $AUC_{0-24h}$ ) was comparable between IM (80.7 ± 40.2 µg·h/mL) and SC (81.1 ± 22.7 µg·h/mL) routes. In contrast, PO administration resulted in approximately 7-fold lower exposure (11.9 ± 4.8 µg·h/mL).
Bioavailability: Relative to IM administration, the bioavailability of SC administration was 100.4%, while PO administration was only 14.8%.
Elimination: The terminal half-life ( $t_{1/2}$ ) progressively increased with the route of administration: IM (9.81 ± 2.30 h) < SC (15.13 ± 4.41 h) < PO (18.85 ± 2.16 h). The difference between IM and PO was statistically significant.

Significance and Claims
The authors claim this study provides the first species-specific pharmacokinetic evaluation of MLX in white storks. The primary significance lies in establishing that SC administration serves as a practical and effective parenteral alternative to IM injection, offering comparable systemic exposure while potentially reducing muscle trauma in rehabilitated birds. Conversely, the study highlights that PO administration in white storks is characterized by low and highly variable bioavailability, suggesting it may not be a reliable route for achieving therapeutic plasma concentrations at standard doses.

The authors note that the progressive prolongation of the apparent terminal half-life from IM to SC to PO suggests "flip-flop kinetics," where absorption rates, rather than elimination rates, govern the terminal phase. They caution that dosing intervals should likely be guided by the IM half-life, which may better reflect true elimination. Furthermore, the study underscores the critical need for species-specific pharmacokinetic data in avian medicine, as findings in white storks (a slow eliminator with low oral bioavailability) cannot be reliably extrapolated from other avian taxa.

Limitations
The paper acknowledges several limitations: the absence of an intravenous reference group prevents the calculation of absolute bioavailability and true clearance/volume of distribution; the 24-hour sampling window may not have fully captured the terminal elimination phase for all individuals; and the study was limited to single-dose administration in clinically stable, non-releasable adults, leaving repeated-dose safety and pharmacokinetics in diseased or juvenile birds unknown. The mechanistic explanations for low oral bioavailability (e.g., intestinal efflux, first-pass metabolism) remain hypothetical and require further investigation.