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  • Author or Editor: Robert P. Hunter x
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Abstract

Alzheimer disease (AD) is the leading cause of dementia among older adults. Current AD treatment options are limited, and the absence of appropriate research animals has significantly hindered the development of new AD therapies. Canine cognitive decline (CCD) is a major determinant of morbidity in older animals, with alterations in blood biomarkers, neuropathology, physiology, and behavior comparable to those seen in humans diagnosed with dementia and AD.

The one-health goal of achieving optimal health is supported by academics, researchers, and governments. Veterinarians’ ability to identify patients in the early stages of CCD is crucial to the successful implementation of interventions that can improve the quality of life of affected dogs. Timely identification of CCD also opens opportunities for innovative interdisciplinary research that will contribute to a better understanding of the underlying mechanisms, early detection, and effective treatments for AD, ultimately benefiting human health as well.

Until now, veterinary practitioners have played limited roles as interdisciplinary leaders in the One Health initiative to combat disease. The authors discuss how client-owned animals with spontaneous, naturally occurring CCD can play a significant role as disease-relevant surrogates for translational AD research. The proposed Dogs Overcoming Geriatric Memory and Aging (DOGMA) Study to be conducted in veterinary practices will analyze the relationship between blood biomarkers and biometric behavior in mature and older dogs, with the aim of establishing benchmark CCD data. The DOGMA Study is addressed in the companion Currents in One Health by Hunter et al, AJVR, November 2023.

Open access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus).

Animals—5 adult Asian elephants.

Procedure—Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis.

Results—The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration.

Conclusion and Clinical Relevance—Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined. (Am J Vet Res 2003;64:109–114)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To describe the pharmacokinetics of cyclosporine (CyA) in healthy dogs after oral administration alone or in combination with orally administered cimetidine.

Animals—10 healthy adult Beagles.

Procedure—Dogs were randomly assigned to receive CyA alone or CyA in combination with cimetidine. After a washout period of 2 weeks, dogs then received the alternate treatment. The CyA plus cimetidine treatment required administration of cimetidine (15 mg/kg of body weight, PO, q 8 h) for 8 days and administration of CyA (5 mg/kg, PO, q 24 h) on days 6 through 8. The CyA treatment alone required administration of CyA (5 mg/kg, PO, q 24 h) for 3 days. On the third day of CyA administration during each treatment, blood samples were collected immediately before (time 0) and 0.5, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 11, 13, 15, 21, and 24 hours after initiating CyA administration.

Results—Time until maximum CyA concentration was significantly longer for CyA in combination with cimetidine. Assessment of estimated pharmacokinetic variables revealed a significantly faster rate of change in the distribution phase for CyA in combination with cimetidine. Maximum CyA concentration differed significantly among dogs but did not differ significantly between treatments.

Conclusions and Clinical Relevance—Analysis of our data suggests that cimetidine may affect absorption of orally administered CyA, but overall, it does not affect the pharmacokinetics of CyA. There is considerable variability in the maximum concentration of CyA among dogs, and monitoring of blood concentrations of CyA during treatment is advised. (Am J Vet Res 2001;62:1046–1050)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period.

Animals—8 healthy 9-month-old female New Zealand White rabbits.

Procedures—Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods.

Results—After oral administration, mean ± SD area under the curve was 10.50 ± 2.00 μg·h/mL and 10.90 ± 2.45 μg·h/mL, maximum plasma concentration was 1.73 ± 0.35 μg/mL and 2.56 ± 0.71 μg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively.

Conclusions and Clinical Relevance—Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.

Full access
in American Journal of Veterinary Research

Abstract

Treatment options for human dementia remain limited, and additional research is needed to develop and validate translational models. Canine cognitive decline (CCD) is common in older dogs and a major source of morbidity. The decline includes physiological and behavioral changes comparable to those in humans diagnosed with dementia. There are also corresponding changes in plasma neurodegenerative biomarkers and neuropathology. Biomarkers for both human and canine cognitive decline can be used to identify and quantify the onset of behavioral data suggestive of CCD. Successful correlations would provide reference values for the early identification of neurodegeneration in canine patients. This could allow for the subsequent testing of interventions directed at ameliorating CCD and offer translational value leading to safe and effective treatment of dementia in people. Research can help exploit, track, and provide benefits from the rapid progression of spontaneous naturally occurring CCD in a large heterogenous community of companion dogs. Research efforts should work to deliver information using blood biomarkers, comorbidities, and wearable technologies to track and evaluate biometric data associated with neurodegeneration and cognitive decline that can be used by both human and companion animal researchers. The synergistic approach between human and veterinary medicine epitomized in one health underscores the interconnectedness of the well-being of both species. Leveraging the insights gained from studying CCD can not only lead to innovative interventions for pets but will also shed light on the complex mechanisms of human dementia.

Open access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons ( Python regius ) after IV or oral administration of a single dose.

Animals—2 male and 5 female ball pythons.

Procedures—Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry.

Results—After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 µg/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration.

Conclusions and Clinical Relevance—Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism. (Am J Vet Res 2003;64:225–228)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws.

Animals—10 healthy blue and gold macaws.

Procedures—In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay.

Results—After oral administration, mean ± SD area under the curve was 7.94 ± 2.08 μg•h/mL, maximum plasma concentration was 1.08 ± 0.316 μg/mL, and bioavailability was 90.0 ± 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 ± 0.32 L/kg, plasma clearance was 0.29 ± 0.078 L/h/kg, area under the curve was 9.41 ± 2.84 μg•h/mL, and the harmonic mean terminal half-life was 4.3 hours.

Conclusions and Clinical Relevance—Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the plasma pharmacokinetics and synovial fluid concentrations after oral administration of single and multiple doses of celecoxib in Greyhounds.

Animals—7 adult Greyhounds.

Procedure—Dogs received celecoxib (median dose, 11.8 mg/kg [range, 11.5 to 13.6 mg/kg], PO, q 24 h) for 10 days. Blood samples were collected prior to administration of celecoxib and serially for 24 hours after the 1st and 10th doses were administered. A synovial joint catheter was placed into a stifle joint in each dog for collection of synovial fluid samples. Concentrations of celecoxib in plasma and synovial fluid were quantified by use of a validated liquid chromatography/mass spectrometry method. Identification of hydroxy- and carboxyl-celecoxib in plasma and synovial fluid was also performed. Pharmacokinetic parameters were determined by use of noncompartmental analysis.

Results—Administration of multiple doses of celecoxib resulted in a significant decrease (40%) in median area under the curve (AUC) values and a corresponding decrease in median maximum concentrations (Cmax; 2,620 to 2,032 ng/mL) between the 1st and 10th doses. Synovial fluid concentrations were less than the corresponding plasma concentrations at all times except 24 hours after administration of the 10th dose of celecoxib.

Conclusions and Clinical Relevance—Celecoxib distributes into the synovial fluid of Greyhounds. Although the exact mechanism for the decreases in AUC and Cmax is not known, results suggested that the plasma pharmacokinetics of celecoxib are different after administration of multiple doses in Greyhounds. These findings warrant further investigation on the absorption, distribution, metabolism, and elimination of celecoxib in Greyhounds and other breeds of dogs. (Am J Vet Res 2005;66:1441–1445)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine plasma pharmacokinetics of penciclovir following oral and rectal administration of famciclovir to young Asian elephants (Elephas maximus).

Animals—6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg.

Procedures—Famciclovir was administered orally or rectally in accordance with an incomplete crossover design. Three treatment groups, each comprising 4 elephants, received single doses of famciclovir (5 mg/kg, PO, or 5 or 15 mg/kg, rectally); there was a minimum 12-week washout period between subsequent famciclovir administrations. Serial blood samples were collected after each administration. Samples were analyzed for famciclovir and penciclovir with a validated liquid chromatography–mass spectroscopy assay.

Results—Famciclovir was tolerated well for both routes of administration and underwent complete biotransformation to the active metabolite, penciclovir. Mean maximum plasma concentration of penciclovir was 1.3 μg/mL at 1.1 hours after oral administration of 5 mg/kg. Similar results were detected after rectal administration of 5 mg/kg. Mean maximum plasma concentration was 3.6 μg/mL at 0.66 hours after rectal administration of 15 mg/kg; this concentration was similar to results reported for humans receiving 7 mg/kg orally.

Conclusions and Clinical Relevance—Juvenile Asian elephants are susceptible to elephant endotheliotropic herpesvirus. Although most infections are fatal, case reports indicate administration of famciclovir has been associated with survival of 3 elephants. In Asian elephants, a dose of 8 to 15 mg of famciclovir/kg given orally or rectally at least every 8 hours may result in penciclovir concentrations that are considered therapeutic in humans.

Full access
in American Journal of Veterinary Research