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Title page: Pharmacokinetics of Cefovecin (Convenia®) After 8 mg/kg Intramuscular Administration in Bottlenose Dolphins (Tursiops truncatus): Age-Related Differences

This study demonstrates that while intramuscular cefovecin (8 mg/kg) provides a prolonged pharmacokinetic profile suitable for long-term antimicrobial therapy in bottlenose dolphins, neonates exhibit significantly shorter elimination half-lives and durations above the therapeutic threshold compared to adults, indicating that dosing intervals should be adjusted based on age.

Original authors: Teresa Encinas, Pablo Morón-Elorza, Carlos Rojo-Solís, Teresa Álvaro, Mónica Valls, Juan A. Gilabert, Daniel García-Párraga

Published 2026-08-20

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Teresa Encinas, Pablo Morón-Elorza, Carlos Rojo-Solís, Teresa Álvaro, Mónica Valls, Juan A. Gilabert, Daniel García-Párraga

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

In the world of veterinary medicine, treating wild or semi-wild animals presents a unique set of hurdles that do not exist in a standard clinic. For a dolphin living in a managed facility, a routine medical check is not a simple matter of walking into an exam room; it requires the animal to be restrained, often out of the water, which induces significant stress. This stress can be dangerous, particularly for newborns, where the physical strain of being handled can lead to injury or even death. Because of this, veterinarians are constantly searching for medicines that work effectively with as few interventions as possible. The ideal drug would be one that stays active in the body for a long time, allowing a single injection to protect an animal for weeks, thereby sparing it from the trauma of repeated captures.

One such drug is cefovecin, an antibiotic already well-known for its ability to linger in the bodies of dogs and cats, where it can provide protection for up to two weeks from a single shot. This long-lasting quality is due to how the drug binds tightly to proteins in the blood and how the kidneys handle it, slowing its exit from the body. However, biology is rarely uniform across species. What works perfectly for a domestic pet might vanish quickly from a bird or a reptile, or linger far too long in a different mammal. Before doctors can safely use this powerful tool on dolphins, they need to know exactly how the drug behaves in these specific marine mammals and whether the animal's age changes the equation.

A team of researchers set out to answer these questions by studying bottlenose dolphins in five different facilities across Europe. They administered a standard dose of the antibiotic, 8 milligrams per kilogram of body weight, into the muscle of seventeen dolphins ranging from newborns just days old to adults in their late twenties. One newborn received a higher dose to see if a larger amount would change how long the drug lasted. The team then carefully tracked the levels of the drug in the dolphins' blood over the course of thirty-five days, taking samples at regular intervals to map out the drug's journey through the body.

The results revealed that cefovecin is indeed a long-acting antibiotic for bottlenose dolphins, but with a notable twist depending on the animal's age. In the adult and subadult dolphins, the drug remained at effective levels for a median of nearly nineteen days. This duration is impressive and suggests that for mature animals, a single injection could cover a significant portion of a month, drastically reducing the need for repeated handling. However, the newborn dolphins told a different story. In this younger group, the drug cleared from the system much faster, remaining at effective levels for only a median of thirteen days. The elimination half-life, a measure of how long it takes for the drug concentration to drop by half, was also significantly shorter in the neonates, lasting about two and a half days compared to nearly four days in the adults.

The researchers also looked at a single juvenile dolphin, which showed a mix of these traits, with a duration of effectiveness falling between the adults and the newborns. When they tested a double dose on one newborn, the peak level of the drug in the blood went up, but the time it stayed above the necessary effective level did not get any longer. This finding is crucial because it rules out the idea that simply giving more of the drug will extend its protective window. For antibiotics like this one, the length of time the drug stays in the system matters more than how high the concentration spikes, meaning that increasing the dose does not solve the problem of the drug leaving the body too quickly in young animals.

These differences likely stem from the physiological immaturity of the newborns. Young dolphins have a higher proportion of water in their bodies and lower levels of the blood proteins that usually hold onto the drug, which may allow it to wash out of their systems more rapidly. Their kidneys, which play a key role in how long the drug stays in the body, may also not yet be fully developed to reabsorb the medication and keep it circulating as efficiently as they do in adults. While the drug still provided a valuable two-week window of protection for the newborns, the data suggests that veterinarians cannot rely on the same schedule for a calf as they would for an adult.

The study concludes that cefovecin is a viable and valuable option for treating dolphins, offering a way to deliver broad-spectrum antibiotic protection with minimal stress. For adult and subadult dolphins, a dosing interval of two to three weeks appears appropriate. For newborns, however, the shorter duration of effectiveness suggests that the interval should be shortened to ten to fourteen days to ensure continuous coverage. This research highlights that while a drug may work well across species, the specific biology of the animal, especially its age, dictates exactly how it should be used. By understanding these nuances, veterinarians can optimize treatment plans that are not only medically sound but also prioritize the welfare of these intelligent and sensitive creatures.

Technical Summary: Pharmacokinetics of Cefovecin in Bottlenose Dolphins

Problem Statement
The administration of antimicrobials in marine mammals, particularly bottlenose dolphins (Tursiops truncatus), presents significant challenges due to the stress associated with repeated handling and restraint, which can lead to injury, maternal rejection, or mortality, especially in neonates. While oral administration is preferred, injectable routes are often necessary when oral absorption is compromised. However, frequent injections exacerbate stress and welfare risks. Cefovecin, a third-generation cephalosporin approved for dogs and cats, offers a potential solution due to its exceptionally long elimination half-life in those species (allowing 14-day dosing intervals). Despite its reported high plasma protein binding (>99%) in dolphins, which suggests a prolonged half-life, species-specific pharmacokinetic (PK) data was lacking. Furthermore, the variability of cefovecin kinetics across taxa—from rapid clearance in birds and reptiles to extended retention in pinnipeds—necessitates rigorous, species-specific evaluation before off-label use can be recommended. Crucially, it was unknown whether age-related physiological differences (e.g., renal maturation, body composition) in dolphins would alter the drug's efficacy or required dosing intervals.

Methodology
This prospective, non-randomized, opportunistic pharmacokinetic study involved 18 bottlenose dolphins from five European zoological facilities. The cohort included 10 adults/subadults, 1 juvenile, and 7 neonates.

Drug Administration: Cefovecin sodium (Convenia®) was administered intramuscularly (IM) into the longissimus dorsi muscle. The standard dose was 8 mg/kg for 17 animals. One neonate received a double dose (16.6 mg/kg) to evaluate dose escalation effects.
Sampling: Blood samples were collected via the ventral superficial fluke plexus at baseline (t=0) and serially over a 35-day period. Thirteen animals provided sufficient serial samples for individual non-compartmental pharmacokinetic analysis; four additional animals provided limited "opportunistic" data points for supportive clinical context.
Analysis: Plasma concentrations were quantified using a validated high-performance liquid chromatography (HPLC) method with UV detection. Pharmacokinetic parameters (elimination half-life [ $t_{½\beta}$ ], $C_{max}$ , $t_{max}$ , AUC, Mean Residence Time [MRT], Volume of Distribution [ $V_d$ ], and Clearance [$Cl$]) were estimated using PK Solution 2.0® software.
Statistical Approach: Data were presented as medians and interquartile ranges due to small sample sizes and non-normal distribution. Differences between age groups (adults/subadults vs. neonates) were assessed using the Mann-Whitney U test. The study utilized a reference MIC $_{90}$ of 1 µg/ml based on common small animal pathogens, acknowledging the lack of species-specific dolphin pathogen MIC data.

Key Results
The study confirmed that cefovecin exhibits a prolonged pharmacokinetic profile in bottlenose dolphins, though with distinct age-related variations:

Adults/Subadults: The median elimination half-life ( $t_{½\beta}$ ) was 3.91 days. Plasma concentrations remained above the MIC $_{90}$ (1 µg/ml) for a median duration of 19.30 days.
Neonates: Neonates exhibited significantly faster elimination. The median $t_{½\beta}$ was 2.50 days ( $p=0.001$ ), and the duration above the MIC $_{90}$ was significantly shorter at 13.00 days ( $p=0.009$ ).
Juvenile: The single juvenile individual showed an intermediate duration above the MIC $_{90}$ (16.00 days) but an elimination half-life (2.42 days) similar to neonates.
Dose Escalation: In the neonate receiving 16.6 mg/kg, the peak plasma concentration ( $C_{max}$ ) increased (49.67 µg/ml vs. ~29 µg/ml in others), but the duration of time above the MIC $_{90}$ did not extend (remained at 12 days).
Safety: No adverse reactions or local injection site reactions were observed.

Significance and Claims
The paper claims that cefovecin administered at 8 mg/kg IM is a viable long-acting antimicrobial option for bottlenose dolphins, offering the potential to reduce handling frequency and associated stress. The study establishes that while the drug provides extended therapeutic coverage, age is a critical variable.

Therapeutic Recommendations: The authors propose a dosing interval of 2–3 weeks for adults and subadults, whereas neonates may require a shorter interval of 10–14 days to maintain continuous therapeutic coverage.
Mechanistic Insight: The shorter duration in neonates is attributed to physiological factors such as immature renal function, higher body water content, and potentially lower plasma protein binding capacity, which may increase the unbound fraction of the drug and facilitate faster clearance.
Dose Escalation Limitations: The study explicitly concludes that increasing the dose is not an effective strategy for extending the dosing interval in neonates, as cefovecin is a time-dependent antibiotic where efficacy relies on the duration above MIC rather than peak concentration.
Comparative Context: The PK profile in dolphins (median $t_{½\beta}$ ~3.9 days) is intermediate between the very long retention seen in pinnipeds (sea lions, walruses) and the shorter retention in other marine mammals like sea otters. This suggests that cetaceans, despite being phylogenetically distinct from carnivores, share some PK characteristics with carnivores regarding cefovecin retention, likely due to high plasma protein binding.

The authors maintain a modest stance, noting that the use of a generic MIC $_{90}$ for small animal pathogens is a limitation and that species-specific MIC data for dolphin-associated pathogens is required to fully refine dosing recommendations. Nevertheless, the study provides the first evidence-based PK characterization of cefovecin in this species, supporting its use as a single-intervention treatment protocol to improve animal welfare.

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