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Abstract

OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized.

ANIMALS 7 male domestic shorthair cats.

PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens.

RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens.

CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess the intraoperative and postoperative clinical effects and histologic effects of intracameral administration of α-chymotrypsin in clinically normal dogs undergoing standard intracapsular lens extraction (ICLE).

Animals—6 young adult male dogs without evidence of systemic or ocular disease.

Procedures—All dogs underwent bilateral ICLE 7 minutes following injection of 75 U of α-chymotrypsin or an identical volume (0.5 mL) of a commercially available balanced saline solution (BSS) into the posterior chamber of the eye. Ease of lens extraction was subjectively assessed and intraoperative intraocular hemorrhage and fibrin accumulation scored. For 27 days after surgery, ocular hyperemia and discharge, chemosis, corneal edema, hyphema, and aqueous flare were scored, and intraocular pressure (IOP) was measured. Thirty days after surgery, histologic evidence of anterior synechia, collapse of and inflammation within the iridocorneal angle, and iritis were scored.

Results—In 5 of 6 dogs, the surgeon was able to correctly identify the eye treated with α-chymotrypsin on the basis of ease of lens extraction. Mean intraoperative intraocular hemorrhage and fibrin scores for BSS-treated eyes were significantly higher than for α-chymotrypsin-treated eyes. Postoperatively, there were no significant differences between treatments for any clinical variables, including IOP Histologic scores were not significantly different between treatments for any variable. Vision was lost as a result of glaucoma in 1 α-chymotrypsin-treated eye and 1 BSS-treated eye.

Conclusions and Clinical Relevance—Intracameral administration of 75 U of α-chymotrypsin 7 minutes before ICLE facilitated lensectomy without apparent adverse effects in clinically normal dogs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate the pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or IV infusion of penciclovir.

Animals—6 cats.

Procedures—Cats received famciclovir (40 [n = 3] or 90 [3] mg/kg, PO, once) in a balanced crossover-design study; the alternate dose was administered after a ≥ 2-week washout period. After another washout period (≥ 4 weeks), cats received an IV infusion of penciclovir (10 mg/kg delivered over 1 hour). Plasma penciclovir concentrations were analyzed via liquid chromatography-mass spectrometry at fixed time points after drug administration.

Results—Mean ± SD maximum plasma concentration (Cmax) of penciclovir following oral administration of 40 and 90 mg of famciclovir/kg was 1.34 ± 0.33 μg/mL and 1.28 ± 0.42 μg/mL and occurred at 2.8 ± 1.8 hours and 3.0 ± 1.1 hours, respectively; penciclovir elimination half-life was 4.2 ± 0.6 hours and 4.8 ± 1.4 hours, respectively; and penciclovir bioavailability was 12.5 ± 3.0% and 7.0 ± 1.8%, respectively. Following IV infusion of penciclovir (10 mg/kg), mean ± SD penciclovir clearance, volume of distribution, and elimination half-life were 4.3 ± 0.8 mL/min/kg, 0.6 ± 0.1 L/kg, and 1.9 ± 0.4 hours, respectively.

Conclusions and Clinical Relevance—Penciclovir pharmacokinetics following oral administration of famciclovir were nonlinear within the dosage range studied, likely because of saturation of famciclovir metabolism. Oral administration of famciclovir at 40 or 90 mg/kg produced similar Cmax and time to Cmax values. Therefore, the lower dose may have similar antiviral efficacy to that proven for the higher dose.

Full access
in American Journal of Veterinary Research

Abstract

Objective–To determine detection rates for feline herpesvirus type 1 (FHV-1), Mycoplasma spp, fungi, and bacteria in flush samples and biopsy specimens from the nasal cavities of cats with and without chronic rhinosinusitis (CRS).

Design–Prospective study.

Animals–10 CRS-affected cats and 7 cats without signs of respiratory tract disease.

Procedures–Nasal flush samples and biopsy specimens were collected from all cats for bacterial (aerobic and anaerobic), fungal, and mycoplasmal cultures; additional biopsy specimens were collected for virus isolation and polymerase chain reaction (PCR) assay (to detect FHV-1 DNA).

Results–Aerobic bacteria were detected in flush samples from 5 of 7 control cats; culture of flush samples from CRS-affected cats yielded aerobic bacteria (9/10 cats), anaerobic bacteria (3/10), and Mycoplasma spp (2/10). No fungal organisms were isolated from any cat. Potential pathogens were isolated significantly more often from CRS-affected cats than from control cats. Bacterial culture of biopsy specimens yielded aerobic bacteria (2/7 control cats and 4/10 CRS-affected cats) and anaerobic bacteria (2/10 CRS-affected cats). Although FHV-1 was not detected in nasal biopsy specimens from control or CRS-affected cats, FHV-1 DNA was detected via PCR assay in specimens from 4 of 7 control cats and 3 of 10 CRS-affected cats.

Conclusions and Clinical Relevance–Compared with findings in control cats, anaerobic bacteria, Mycoplasma spp, and a variety of potentially pathogenic organisms were detected more commonly in samples from cats with CRS. In both groups, FHV-1 was detected via PCR assay as a nonviable organism or in noncultivable amounts. (J Am Vet Med Assoc 2005;227:579–585)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine prevalence, reason for evaluation, treatment, and outcome for dogs and cats with presumed solitary ocular lymphoma (PSOL).

Design—Retrospective case series.

Animals—7 dogs and 2 cats with PSOL.

Procedures—Medical records were reviewed. Progression-free survival time (PFST) and overall survival time (OST) were determined.

Results—Animals with intraocular (4 dogs and 1 cat) or conjunctival (3 dogs and 1 cat) lymphoma represented 0.1% and 0.08% of patients with lymphoma evaluated at the hospital during the study period, respectively. Animals with intraocular lymphoma represented 0.19% of all patients with uveitis; animals with conjunctival lymphoma represented 0.16% of all patients with conjunctivitis. Tumors included B-cell (2 intraocular and 1 conjunctival), non–B-cell, non–T-cell (1 intraocular), and T-cell (3 conjunctival) neoplasms; immunophenotype of 2 uveal lymphomas was not determined. Treatments included enucleation (4 intraocular) and chemotherapy (3 intraocular and 2 conjunctival). All dogs with intraocular lymphoma developed neurologic signs. Lymph node metastasis was detected in 2 patients with conjunctival lymphoma. Median PFST and OST were 178 days for all animals with PSOL, dogs with PSOL, and animals with intraocular lymphoma. Median PFST and OST for animals with conjunctival lymphoma were 221 and 549 days, respectively.

Conclusions and Clinical Relevance—Results indicated PSOL was uncommon, but should be considered a differential diagnosis for animals with uveitis or conjunctivitis. Performance of MRI and cytologic analysis of CSF and regional lymph node aspirate samples may be beneficial for such patients. Prognosis seemed to be better for animals with conjunctival lymphoma than it was for those with intraocular lymphoma.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare detection rates of feline herpesvirus 1 (FHV-1) DNA in skin biopsy specimens from cats with herpetic dermatitis, cats with nonherpetic dermatitis, and cats without dermatitis.

Design—Prevalence survey.

Animals—5 cats (9 biopsy specimens) with herpetic ulcerative dermatitis, 14 cats (17 biopsy specimens) with nonherpetic ulcerative dermatitis, and 8 cats (21 biopsy specimens) without clinically apparent skin lesions.

Procedures—A single-phase PCR assay was used to detect FHV-1 DNA in biopsy specimens. Assay results were compared with results of histologic examination.

Results—FHV-1 DNA was detected in all 9 biopsy specimens from the 5 cats with herpetic dermatitis and in 1 of 17 biopsy specimens from the 14 cats with nonherpetic dermatitis, but was not detected in any of the 21 biopsy specimens from the 8 cats without dermatitis. When results of histologic examination were used as the gold standard, sensitivity and specificity of the PCR assay were 100% and 95%, respectively.

Conclusions and Clinical Relevance—Results confirmed that FHV-1 DNA can be detected in the skin of cats with herpetic dermatitis and suggest that the virus may play a causative role in the disease. In addition, the PCR assay may be useful in confirming a diagnosis of herpetic dermatitis.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris).

Design—Pharmacokinetic study.

Animals—18 juvenile northern elephant seals without signs of ocular disease.

Procedures—Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography–tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis.

Results—Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 μg/mL at 6.1 hours on day 1 and was 1.5 μg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 μg/mL at 2.3 hours on day 1 and 1.9 μg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing.

Conclusions and Clinical Relevance—Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the distribution and clinical outcome of ocular lesions in snakes.

Design—Retrospective case series.

Animals—67 snakes with ocular lesions.

Procedures—Signalment, lesion duration, diagnosis, treatment, and clinical outcome were recorded for all snakes with ocular lesions that were examined at a veterinary teaching hospital from 1985 to 2010.

Results—71 ocular lesions were detected in 67 of 508 (13%) snakes examined. Affected snakes were of the families Boidae, Pythonidae, Colubridae, and Viperidae. The distribution of ocular lesions did not vary by taxonomic family, age, or sex; however, snakes from the genus Epicrates with ocular lesions were overrepresented in the population. The most commonly diagnosed ocular lesions were retained spectacle (n = 41), pseudobuphthalmos or subspectacular abscess (13), trauma (8), and cataracts (4). Pseudobuphthalmos or subspectacular abscess developed more frequently in Colubridae than in non-Colubridae snakes. Of the 16 snakes with retained spectacles for which data were available, the lesion recurred once in 4 snakes and multiple times in 5 snakes.

Conclusions and Clinical Relevance—Results indicated that retained spectacle was the most common ocular lesion diagnosed in snakes. Compared with other snakes with ocular lesions, snakes of the genus Epicrates had a higher than expected frequency of ocular lesions in general and snakes of the family Colubridae had a higher than expected frequency of pseudobuphthalmos or subspectacular abscess.

Full access
in Journal of the American Veterinary Medical Association

Objective

To determine the value of virus isolation (VI), immunofluorescent antibody (IFA) assay, serum neutralization (SN), and ELISA for the diagnosis of clinical feline herpesvirus-1 (FHV-1) infection in cats.

Animals

46 clinically normal cats, 17 cats with signs of acute respiratory tract disease, and 38 cats with signs of chronic ocular disease.

Procedure

Conjunctival swabs for VI, conjunctival scrapings for IFA testing, and venous blood samples for SN or ELISA testing were obtained from all cats.

Results

FHV-1 was detected in 10.9 and 28.3% of clinically normal cats and in 18.2 and 33.3% of cats with FHV-1-associated disease by VI and the IFA assay, respectively. There were no significant differences in the viral detection rate between cats with acute respiratory tract disease and cats with chronic ocular disease or between diseased cats and clinically normal cats; however, FHV-1 was never detected by both methods in clinically normal cats. Overall FHV-1 seroprevalence was 97% when tested by ELISA and 66% when tested by SN. Seroprevalence did not vary significantly among the 3 groups for either serologic test. Magnitude of SN and ELISA titers varied greatly but independently of presence or absence of clinical signs of FHV-1-associated disease. Sensitivity, specificity, and positive and negative predictive values were assessed for VI and the IFA assay—jointly and individually—and for each SN and ELISA titer magnitude. Values never all exceeded 50%.

Clinical Implications

Because FHV-1 can be detected commonly in clinically normal cats by the IFA assay or VI, neither test appears to aid in the clinical diagnosis of FHV-1 infection. Seroprevalence does not appear to vary between affected and clinically normal cats. SN, ELISA, VI, and the IFA assay appear to be of limited value in the diagnosis of FHV-1-associated disease in cats. Concurrent assessment of the IFA assay and VI results may permit exclusion of FHV-1 as an etiologic agent if results of both tests are negative. (J Am Vet Med Assoc 1999;214:502–507)

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine within a cat shelter effects of dietary lysine supplementation on nasal and ocular disease and detection of nucleic acids of Chlamydophila felis, feline calicivirus (FCV), and feline herpesvirus (FHV-1).

Animals—261 adult cats.

Procedures—Cats were fed a diet containing 1.7% (basal diet; control cats) or 5.7% (supplemented diet; treated cats) lysine for 4 weeks. Plasma concentrations of lysine and arginine were assessed at the beginning (baseline) and end of the study. Three times a week, cats were assigned a clinical score based on evidence of nasal and ocular disease. Conjunctival and oropharyngeal swab specimens were tested for FHV-1, FCV, and C felis nucleic acids once a week.

Results—Data were collected from 123, 74, 59, and 47 cats during study weeks 1, 2, 3, and 4, respectively. By study end, plasma lysine concentration in treated cats was greater than that in control cats and had increased from baseline. There was no difference between dietary groups in the proportion of cats developing mild disease. However, more treated cats than control cats developed moderate to severe disease during week 4. During week 2, FHV-1 DNA was detected more commonly in swab specimens from treated versus control cats.

Conclusions and Clinical Relevance—Dietary lysine supplementation in the amount used in our study was not a successful means of controlling infectious upper respiratory disease within a cat shelter. Rather, it led to increases in disease severity and the incidence of detection of FHV-1 DNA in oropharyngeal or conjunctival mucosal swab specimens at certain time points.

Full access
in American Journal of Veterinary Research