Evaluation of transdermal morphine and fentanyl pluronic lecithin organogel administration in dogs

Transdermal administration of morphine and fentanyl using a pluronic lecithin organogel was evaluated in dogs. IV administration of morphine and fentanyl resulted in therapeutic serum drug concentrations. Following transdermal administration, however, median serum drug concentrations were never above the limit of quantitation for morphine or fentanyl. These findings indicate that use ofa pluronic lecithin organogel for transdermal administration of morphine or fentanyl cannot be justified.     

抗小鹅瘟卵黄抗体脱脂方法研究

通过对产蛋母鸡免疫接种小鹅瘟JS1株油乳荆灭活苗,从而获得含高效价小鹅瘟病毒抗体的鸡蛋.采用聚乙二醇6000和泊洛沙姆进行脱脂试验,并优化脱脂条件.结果表明,聚乙二醇6000和泊洛沙姆对鸡卵黄具有良好的脱脂作用,其中聚乙二醇6000价格低廉,更适合大规模工业化生产.     

A Comparison of Antimicrobial Efficacy and Tissue Reaction of Four Antiseptics on Canine Wounds

Three concentrations of povidone iodine, chlorhexidine, benzalkonium chloride, and a pluronic polyol were tested for antimicrobial efficacy and tissue reaction in wounds inoculated with Staphyloccocus aureus .
Five paired incisions were created on the back of each of 16 dogs in four treatment groups. Five wounds were inoculated with beta-hemolytic, coagulase positive S. aureus (10⁹ organisms); the contralateral wounds were not inoculated. After two hours, three wounds on each side were irrigated with antiseptic in low, medium, or high concentrations; another was irrigated with physiological saline; and one was left untreated. One hundred ml of solution was applied in each instance with a syringe and needle at approximately 8 psi.
Tissue bacteria were quantitated immediately following irrigation. The wounds were sutured with 5/0 monofilament stainless steel and bandaged. After 48 hours, the dogs were euthanized and signs of wound infection were recorded. Wound bacteria were quantitated again, and sections of the wounds were removed for examination by light microscopy.
Antiseptics were significantly effective (p < 0.01) in reducing the bacterial population in contaminated wounds when compared to control wounds on the same dog. High antiseptic concentrations were more effective than low concentrations. At 48 hours, the bacterial population was significantly lower in wounds treated with chlorhexidine or benzalkonium chloride compared with povidone iodine or pluronic polyol. The antiseptics caused no significant difference (p < 0.01) in tissue reaction in noninoculated wounds. Chlorhexidine (0.5 or 1.0%) was the most effective antiseptic under the conditions used.     

Systemic absorption of amitriptyline and buspirone after oral and transdermal administration to healthy cats

A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzyme-linked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.     

Comparison of serum dexamethasone concentrations in cats after oral or transdermal administration using pluronic lecithin organogel (PLO): a pilot study

The objective of this study was to measure and compare the serum concentrations of dexamethasone after oral and transdermal administration using pluronic lecithin organogel in six healthy cats. The study was designed as a crossover, in which the cats were randomly assigned to two groups. The cats received a single dose (0.05 mg kg(-1)) of dexamethasone either orally or transdermally on the inner pinna. Blood samples were taken at 0, 5, 15, 30, 60, 90 and 120 min, and 3, 4, 6, 8, 12 and 24, 48 and 72 h post dexamethasone administration. A mean peak serum concentration of 30.1 ng mL(-1) was detected 15 min after oral administration. Serum concentrations were below detection limits by 24 h. In contrast, there was no significant increase in serum concentrations of dexamethasone after transdermal administration. In cats, transdermal administration of a single dose of dexamethasone did not result in significant serum concentrations compared to oral administration.     

Relationship between plasma concentrations and analgesia after intravenous fentanyl and disposition after other routes of administration in cats

Data allowing rational use of analgesics in cats are limited. Pharmacokinetics and pharmacodynamics of fentanyl were studied in cats. Plasma fentanyl concentrations were measured using radioimmunoassay in a crossover study in six cats after 10 microg/kg (i.v.) or by application of fentanyl in pluronic lecithin organogel (PLO) to the inner ear pinna. On a separate occasion thermal thresholds were measured after i.v. fentanyl (10 microg/kg) or saline. Plasma fentanyl concentrations reached 4.7-8.31 ng/mL 2 min after i.v. administration and were undetectable after 95 min. Fentanyl was not detected in plasma at any time after PLO use. Thermal thresholds did not change following saline administration but were increased above baseline from 5 to 110 min after i.v. fentanyl. In this model a plasma concentration of >1.07 ng/mL was required to provide analgesia. Plasma concentrations were measured in additional cats after intranasal or oral dosing (2 microg/kg) and after 30 microg/kg in PLO gel. After oral and nasal dosing, Cmax values were 0.96 and 1.48 ng/mL at 5 and 2 min, respectively. Plasma fentanyl was not detected after application of the higher dose of fentanyl in PLO.     

Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats

OBJECTIVE: To determine bioavailability, pharmacokinetics, and safety for transdermal (TD) and oral administration of fluoxetine hydrochloride to healthy cats. ANIMALS: 12 healthy mixed-breed sexually intact 1- to 4-year-old purpose-bred cats. PROCEDURE: A single-dose pharmacokinetic study involving 3 groups of 4 cats each was conducted in parallel. Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg. Plasma samples were obtained and submitted for liquid chromatography-mass spectrometry-mass spectrometry analysis of fluoxetine and its active metabolite, norfluoxetine. RESULTS: Peak fluoxetine concentration (Cmax) was lower and time to Cmax longer for TD administration versus oral administration. Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug. Mean plasma elimination half-life after oral administration was 47 and 55 hours for fluoxetine and norfluoxetine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence that fluoxetine in a 15% (wt:vol) PLO gel formulation can be absorbed through the skin of cats into the systemic circulation. However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration.     

Bioavailability of transdermal methimazole in a pluronic lecithin organogel (PLO) in healthy cats

The antithyroid drug methimazole is widely used for the medical management of feline hyperthyroidism. Recently, custom veterinary pharmacies have offered methimazole in a transdermal gel containing pluronic and lecithin (PLO), with anecdotal evidence of efficacy. The purpose of this study was to determine the bioavailability, relative to i.v. and oral routes of administration, of transdermal methimazole in a PLO gel in cats. Six healthy adult cats were assigned to receive 5 mg of methimazole by the i.v., oral, or transdermal routes, in a randomized triple crossover protocol with 1 week washout between doses. Blood samples were taken for high performance liquid chromatography (HPLC) determination of serum methimazole, at 0, 5, 15, 30, 60 min, and 2, 4, 6, 12 and 24 h after dosing. Methimazole absorption following transdermal administration was poor and variable, with only two of six cats achieving detectable serum methimazole concentrations at any time point following transdermal administration. Area under the concentration-time curve (AUC), maximum concentration (Cmax), and absolute bioavailability were all significantly lower for the transdermal route (0.39 +/- 0.63 microg h/mL, 0.05 +/- 0.09 microg/mL, and 11.4 +/- 18.7%, respectively) than for either i.v. (7.96 +/- 4.38 microg h/mL, 3.34 +/- 2.00 microg/mL, 100%) or oral routes (2.94 +/- 1.24 microg h/mL, 0.51 +/- 0.15 microg/mL, 40.4 +/- 8.1%). The results of this study indicate generally low to undetectable bioavailability of methimazole in a lecithin/pluronic gel given as a single transdermal dose to healthy cats, although one individual cat did achieve nearly 100% transdermal bioavailability relative to the oral route.     

Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism

The objective of this study was to determine whether transdermal methimazole was as safe and effective as oral methimazole for the control of hyperthyroidism in cats. Forty-seven cats with newly diagnosed hyperthyroidism were randomized to receive either transdermal methimazole in pluronic lecithin organogel (PLO; applied to the inner pinna), or oral methimazole (2.5 mg q12h for either route). Cats were evaluated at weeks 0, 2, and 4 with a physical exam, body weight determination, CBC, biochemical panel, urinalysis, measurement of total levothyroxine (T4) concentration, indirect Doppler blood pressure determinaiton, and completion of an owner questionnaire. Data between the 2 groups and over time were compared by nonparametric methods. Forty-four cats followed the protocol (17 oral and 27 transdermal). Significantly more cats treated with oral methimazole had serum T4 concentrations within the reference range after 2 weeks (14 of 16 cats) compared to those treated by the transdermal route (14 of 25; P = .027). This difference was no longer significant by 4 weeks of treatment (9 of 11 for oral versus 14 of 21 for transdermal), possibly because of inadequate numbers evaluated by 4 weeks. Cats treated with oral methimazole had a higher incidence of gastrointestinal (GI) adverse effects (4 of 17 cats) compared to the cats treated with transdermal methimazole (1 of 27; P = .04), but no differences were found between groups in the incidence of neutropenia, hepatotoxicity, or facial excoriations. Although the overall efficacy of transdermal methimazole is not as high as that of oral methimazole at 2 weeks of treatment, it is associated with fewer GI adverse effects compared to the oral route.     

Duration of T4 Suppression in Hyperthyroid Cats Treated Once and Twice Daily with Transdermal Methimazole

Background

Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring.

Objective

To assess variation in serum T4 concentration in hyperthyroid cats after once‐ and twice‐daily transdermal methimazole administration.

Animals

Twenty client‐owned cats with newly diagnosed hyperthyroidism.

Methods

Methimazole was formulated in a pluronic lecithin organogel‐based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5 mg/cat q12h (BID group, 10 cats) and 5 mg/cat q24h (SID group, 10 cats). One and 3 weeks after starting treatment, T4 concentrations were measured immediately before and every 2 hours after gel application over a period of up to 10 hours.

Results

Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10‐hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups.

Conclusions

Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response.     

Two cases of disseminated toxoplasmosis

Two cases of disseminated fatal toxoplasmosis of a pet mouse and a red panda are described. The pet mouse had a private owner; the red panda lived in a zoological garden in Saxony. At necropsy, both animals suffered from a systemic toxoplasmosis. A severe necrotizing hepatitis was the main histological feature in both animals. Parasitic cysts could be abundantly found in the liver, moderately in the brain and in a low number in other organs. With the PAS-reaction, cysts showed a weak staining in the mouse and a strong staining in the red panda. Diagnosis was confirmed by PCR and immunohistochemistry.     

Comparison of methods for determining the prececal nutrient digestibility and amino acid absorption of swine with ileorectal anastomoses and ileocecal bridge cannulas]

The apparent precaecal nutrient digestibility and amino acid (a.a.) absorption of 10 diets were estimated in pigs with end-to-side ileorectal anastomoses (IRA) as well as with ileocaecal re-entrant cannulae (IZB). The digestibilities of organic matter and crude carbohydrates were significantly higher in IRA pigs than in IZB pigs in two resp. three diets only. There were no practical important differences for the digestibilities of crude protein and crude fat in all diets. Out of the 180 a.a. absorption comparisons only 20 (i.e. 11%) showed differences larger than 5%-units. The absorption rates of several a.a. were lower in IRA than in IZB pigs and of some other a.a. on the contrary. The methionine absorption of five legume diets and one barley + lysine diet were up to 15% resp. 4%-units lower in IRA pigs. Possibly this was due to the activity of microbes in the rectum in connection with a small intake level of protein bound methionine. In order to minimize such a falsification it is proposed to use the end-to-end anastomosis. The deviations in the apparent a.a. absorption between IRA and IZB pigs can be explained partly by differences in the quantity of precaecally excreted endogenous a.a. per 100 g DM intake.     

Human Dirofilaria repens infection in Hungary: a case in the spermatic cord and a review of the literature

Orchiectomy was performed in a 37-year-old Hungarian man exhibiting a swelling in his right testicle. Histology revealed a nodule attached to the spermatic cord, consisting of a granulomatous tissue around sections of a nematode. The worm was identified as Dirofilaria repens, an uncommon parasite in Hungary. As the patient had been abroad only in Italy where cases of dirofilariosis in dogs and humans are relatively frequent, it is assumed that the infection might have been acquired in that country 5 years earlier. This is the fifth case, published so far in the world, of such a localization in a human. The human cases of dirofilariosis reported in Hungary are reviewed.     

Gammaherpesvirus infection in a free-ranging eastern grey kangaroo (Macropus giganteus)

A gammaherpesvirus was detected by polymerase chain reaction (PCR) in ocular, nasal and oropharyngeal swab samples collected from an adult free-ranging male eastern grey kangaroo (Macropus giganteus) with clinical signs of severe respiratory disease. This is the first time a gammaherpesvirus has been detected in a free-ranging macropod in Australia. The nucleotide sequence of a conserved region of the DNA polymerase gene of the detected virus showed a high degree of identity to a gammaherpesvirus recently detected in a zoological collection of eastern grey kangaroos in North America. The detection of this gammaherpesvirus in a free-ranging, native eastern grey kangaroo provides evidence that this species is a natural host.     

Tibial hemimelia, meningocele, and abdominal hernia in Shorthorn cattle

Six genetically related Shorthorn calves were affected with the tibial hemimelia syndrome. The lesions included bilaterally malformed or absent tibia and abdominal hernia in all animals, a long shaggy haircoat, retained testicles in males, and meningocele in three animals. The malformations were similar to those described previously in Galloway calves. Pedigree analysis demonstrated a mechanism by which a recessive allele in a homozygous state could be responsible for the disorder. The condition in these calves was considered the result of a recurrence of a genetic mutation affecting a putative hemimelia locus.     

Preliminary experiences with the treatment of shock in horses with a plasma expander from a starch base

HAES Steril 10% is a colloidal plasma expander rarely used in veterinary medicine. In this study HAES was used in clinical cases for the treatment of shock and in a comparative hypervolemic hemodilution study (HAES versus lactated Ringer's solution) using two experimental horses. Injection of a HAES volume equivalent to 10% of estimated blood volume resulted in a highly significant drop in PCV and in a significant drop in total protein concentration. Half live of HAES was approximately two hours. No incompatibility reactions were observed. In man HAES improves microcirculation. Studies in progress may confirm a similar effect in the equine.     

Bovine viral diarrhea virus isolated from fetal calf serum enhances pathogenicity of attenuated transmissible gastroenteritis virus in neonatal pigs.

A bovine viral diarrhea virus (BVDV-C) was isolated from swine tissue culture cells used to attenuate the transmissible gastroenteritis virus (TGEV) after 68 passes. Piglets given a pure culture of BVDV-C developed clinical signs similar to those of a mild TGEV infection and recovered by 10 days postexposure. Villous blunting and fusion was observed in the small intestine, and a lymphocyte depletion was observed in Peyer's patches in the ileum. Piglets given a combination of BVDV-C and attenuated TGEV developed clinical signs similar to those of a virulent TGEV infection and were euthanized. The combined infection induced a generalized lymphocyte depletion throughout the lymphatic system and villous atrophy in the intestinal tract. Piglets exposed to a another type I strain of BVDV (NY-1) either alone or in combination with the attenuated TGEV had mild clinical signs similar to those of a TGEV infection. Moderate villous atrophy in the ileum and a lymphocyte depletion in the mesenteric lymph node were observed in these piglets postmortem. The data indicate a potential problem for diagnostic laboratories in relation to a diagnosis of virulent TGEV infections and in the field for young piglets exposed to a BVDV-contaminated TGEV vaccine.     

Devitalizing effect of Jodonal A in vitro on bacteria subject to a short-term exposure]

In a three-minute exposure in vitro Jodonal A devitalized a culture of serological group B streptococci in a 2% concentration, Staphylococcus aureus in a 16% concentration, Pneumococcus in a 4.5% concentration, Corynebacterium pyogenes in a 2.5% concentration, Pseudomonas aeruginosa in a 3% concentration, and Klebsiella pneumoniae in a 2% concentration. Hence Jodonal A concentrations higher than 16% should be tested for udder teat disinfection after the removal of teat cups.     

The peri-parturient rise in sheep. Faecal worm egg counts in normal and late lambing ewes

The trichostrongylid and strongylid egg output in a group of ewes lambing in March, the middle of the usual lambing time in the Netherlands, was compared with counts in groups of older ewes and yearling ewes lambing in May-June and with counts in a group of barren ewes. The groups lambing in March showed only a rise related to parturition date as normally seen in the Netherlands. A few of the late lambing ewes showed a slight rise in spring, but all of them showed a peri-parturient rise related to parturition date. In the late lambing ewes and in the barren ewes egg counts due to reinfection were seen in summer. It is concluded that under the present circumstances a true spring rise, the calendar phenomenon, occurs very irregularly, while a peri-parturient rise related to the parturition date is a common phenomenon. The occurence of high egg counts in summer, excluding consideration on the barren ewes, in the late lambing ewes only, suggests that changing the traditional husbandry system may influence the epidemiological pattern of the trichostrongylid infections.     

Spontaneous neoplasms in captive African cane rats (Thryonomys swinderianus Temminck, 1827)

Despite the increasing importance of cane rat (Thryonomys swinderianus) farming in Africa, diseases of these animals in captivity are not well known. A survey of a colony in Gabon averaging 235 cane rats over a period of 36 months allowed the observation of several suspected tumors and the confirmation of three cases of neoplasms. Within a period of 8 months, a chondroma in an adult female, a hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female were diagnosed. This incidence (1.3%) of neoplasms in the cane rat colony in such a short period is uncommon. Neoplasms in rodents might be induced by such factors as a high inbreeding coefficient, an oncogenic virus, or chemical agent intoxication. Although the etiology remains undetermined, these cases are described to provide baseline data on the pathology of this species in captivity.