136 research outputs found
Dr. Boothe in Laboratory
No full textDr. Dawn M. Boothe in the Veterinary Pharmacology and Physiology Laboratory. Physical description: color prints (photographs), 11.5X17mmDr. Dawn M. Boothe received a B.S. in Zoology in 1977 and 1978 a B.S. in Veterinary Medicine. She completed her D.V.M. in 1980, and her M.S. in Physiology in 1986 from Texas A&M University. In 1981 she had an internship at Auburn University, College of Veterinary Medicine in their Small Animal Surgery and Medicine department. Later in 1985 she worked in the residency program at Texas A&M, College of Veterinary Medicine in Small Internal Medicine Department. Dr. Boothe completed her Ph.D. and fellowship in the field of Physiology, Clinical Pharmacology here at Texas A&M in 1989. She has received several teaching awards and serves as a Diplomate for the American Colleges' of Veterinary- (Internal Medicine) and (Clinical Pharmacology), respectively.
Dr. Dawn Boothe, as of 2017 was the Director of the Clinical Pharmacology Laboratory at Auburn University, College of Veterinary Medicine; and assists the faculty that teaches Veterinary Pharmacology to second-year veterinary students
Development and validation of a UPLC-MS method for quantification of selected cannabinoids in canine plasma and its application to commercial cannabis products
No full textIntroduction. Cannabinoids are the important chemicals in cannabis plant with medicinal value [51]. However, effective and safe use is best based on studies that describe their behavior in the plasma of the species being treated. This requires a method for accurate and precise quantification of these closely chemically related compounds. Several LC-MS and GC-MS methods have been described in the literature that quantify cannabinoids in human plasma, rat urine, waste water, surface water, cannabis plant, and cannabis oil. However, the quantification of cannabinoids in canine plasma has not being described. This study describes the development and validation of a reverse phase ultra-performance liquid chromatographic (UPLC) method with mass spectrometry (MS) detection using solid phase extraction for the simultaneous determination of the major cannabinoids. (cannabidiol, tetrahydrocannabinol cannabigerol, cannabinol, and cannabichromene) in canine plasma.
Methods. Based on the chemical structures, physical properties, sample type (canine plasma), and previously reported methods, an analytical method was developed and validated using solid phase extraction to clean up the sample, liquid chromatography for separation and tandem mass spectrometry (LC-MS/MS) for detection.
Results. Cannabinoids were extracted from canine plasma by using Oasis HLB SPE cartridges. Cannabinoids detection, separation and quantification was accomplished using a C18 chromatographic column, a mobile phase consisting of formic acid in water and acetonitrile at a flow rate of 0.5 mL/min. LC-MS/MS with Electrospray ionization (ESI) in positive mode and multiple reaction monitoring (MRM) was used for quantification. The limit of detection (LOD) for the five major cannabinoids was 1.95 ng/mL. The lower limit of quantification (LLOQ) for cannabidiol, and tetrahydrocannabinol was 3.91 ng/mL. For cannabidiol the mean accuracy (% recovery) was 100% ± 18% with a 16% Precision. For tetrahydrocannabinol the mean accuracy (% recovery) was 105% ± 5% with a 5% Precision. Using this method, both cannabidiol and tetrahydrocannabinol were detected and quantified in the plasma of canine patients receiving commercial cannabis-based products. The analytical method for the analysis of cannabinoids in commercial products will require a future validation
Conclusions. We have successfully validated a cannabinoid LC-MS/MS method for quantitation of cannabidiol and tetrahydrocannabinol in canine plasma. This assay will support clinical trials and pharmacokinetic studies necessary to demonstrate safety and efficacy of these promising agents. Identification of cannabigerol, cannabinol, and cannabichromene in canine plasma can be performed with this method, but validation is still pending
The stability of enrofloxacin
No full textDigitized from print original stored in HDR. Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.Program year: 1997/1998Enrofloxacin is an antimicrobial drug approved for veterinary use only. Enrofloxacin is administered orally or parenterally. Veterinarians may dilute the drug for injection or topical use in a commercial physiological solution. The injectable commercially used Enrofloxacin, Baytril, is sometimes too strong, causing vomiting, and much smaller concentrations are effective topically. It is hypothesized that the dilution of enrofloxacin in some commercially used solutions will not affect the drug's efficacy. The purpose of my study was to test the afore stated hypothesis. In the experiment, stock solutions of enrofloxacin in physiological saline solution, dextrose 5% in water, lactated Ringer's solution, Epi-otic solution, and vinegar. E. coli 2592-2 (standardized solution in saline) was the microorganism chosen to be tested because it is known to be susceptible to enrofloxacin. At time 0, 1 day and 7 days and temperatures of 25��C and 4��C, decreasing tube dilutions (0.125 to 16 ��g/ml) of each stock solution and a standard enrofloxacin solution (control) were made using Mueller-Hinton broth. Each dilution of the enrofloxacin solution and an equal amount of bacterial solution were combined and incubated for 24 hours. The resulting growth was read using ultraviolet spectrophotometry and the minimum inhibitory concentration (MIC) of enrofloxacin in each solution was determined and compared to the control. Results showed that the MIC's at time ��� were: control - 8 ��g/ml, saline - 0.25 ��g/ml, dextrose - 4 ��g/ml, ringer - 1 ��g/ml, epi-otic - 4 ��g/ml, and vinegar - 2 ��g/ml. The results for both temperatures at 1 day followed the same pattern. At 7 days, crystals of enrofloxacin were observed in all solutions at both temperatures, hence these solutions were not tested by tube dilution. Therefore, it can be concluded that because the commercial solutions caused a decrease in MIC, they all appear to increase rather than decrease the efficacy of enrofloxacin. The experiment shows that some physiological solutions can alter the efficacy of enrofloxacin when the two are combined for clinical use, but this alteration is favorable
Impact of Antimicrobial Therapy on Fecal Escherichia coli in Dogs
No full textAntimicrobial resistance is an emerging aspect of antimicrobial therapy. However, few studies have documented this relationship in vivo. The purpose of this study was to describe the relationship between antimicrobial therapy and emerging antimicrobial resistance within the normal flora. The dog was chosen as the model because it is the target species to which therapy is directed and it has a close relationship to humans. Fecal E. coli were chosen as the sentinel organism because of ease of access, the fast reproductive time, high rate of mutability and it is the common cause of disease, particularly urogenital, in dogs and humans. Amoxicillin and enrofloxacin were chosen
as the target drugs because they are common choices for treatment of E. coli associated disease and different resistance mechanisms were anticipated.
We hypothesized that amoxicillin resistance would be short-lived, oriented toward beta-lactams and plasmid mediated, whereas enrofloxacin resistance would persist, but be limited to enrofloxacin. Amoxicillin or enrofloxacin was administered to 8 healthy, antimicrobial-free purpose-bred dogs; no drug was administered to 8 control dogs until resistance was expressed in their fecal E. coli. The drug was then discontinued and monitoring continued until resistance was either resolved or 28 days had passed. Representative bacterial isolates expressing resistance were collected from each dog per group per time point. Each isolate was serotyped and tested for virulence. Each isolate was characterized for the degree of resistance and whether the resistance was to multiple drugs. In addition, representative isolates from each group were serotyped.
Close to 100% of fecal E. coli isolates rapidly became resistant to both drugs. Amoxicillin resistance resolved in 7-9 days. In contrast, all E. coli were eradicated in 4 dogs receiving enrofloxacin. In the remaining dogs, resistance resolved in 11-21 days but did not resolve in one dog by the end of the study. Resistance to both drugs was at least 16 fold higher than the breakpoint (high level). Resistance associated with enrofloxacin but generally not amoxicillin was multidrug resistance (MDR). Amoxicillin therapy induced resistance to penicillins, selected cephalosporins but not carbapenems. Beta-lactamase resistance was due to TEM β-lactamase (TEM). It was horizontally transferred, with the exception of extended-spectrum β-lactamase enzymes (ESBLs), which were detected only in selected isolates. Amoxicillin therapy induced variable phenotypes and genotypes. One dog receiving amoxicillin developed MDR (including enrofloxacin) resistance. For enrofloxacin treated dogs, genotypes within phenotypes were less variable. All isolates expressed TEM β-lactamase mediated by a non-transferrable mechanism. Resistance to fluoroquinolone (FQ) was mediated by double mutations in both gyrA and parC. Mutation in a global regulator SoxS was found and our data indicate that this oxidative stress response regulator may impact MDR mediated by enrofloxacin in fecal E. coli. Among serotypes, more variety occurred in non-MDR than in MDR or in control dogs, with clonality associated with enrofloxacin but not amoxicillin resistance. Virulence factors were limited to cnf-1 and cnf-2 which were detected in only 5 isolates.
In conclusion, these studies indicated that a high level of antimicrobial resistance rapidly evolved in E. coli from dogs treated with either amoxicillin or enrofloxacin. However, resistance resolved more quickly with amoxicillin, and was associated with multiple drugs for enrofloxacin. Non-ESBL beta-lactamase resistance occurred only with amoxicillin and was transmissable. We report for the first time (1) a substitution of alanine for glutamate at codon 84 of parC gene is associated with enrofloxacin in E. coli and (2) a point mutation leading to a substitution of serine for alanine at codon 12 of a general regulator soxS in MDR is associated with enrofloxacin therapy
Cannabinoid: A Potential Anti-Cancer Agent for Non-Hodgkin Lymphoma
No full textThe non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies and are one of the most commonly diagnosed neoplasm in both dogs and humans. Systemic anticancer chemotherapy is the treatment of choice for human and canine lymphomas. Canine and human lymphoma are generally characterized by a high rate of initial remission following conventional CHOP (cyclophosphamide, hydroxyl-doxorubicin, vincristine, and prednisone) based therapies; however, 95% of dogs and 30% of humans will succumb to drug-resistant relapse and in most cases face severe side effects of chemotherapeutic drugs. Owing to shared molecular, signaling, incidence, and pathologic features, treatment approach and treatment need, studying novel targets for lymphoma treatment in canine can be beneficial for both species.
Cannabis or Marijuana have been used as medicine for centuries. With renewed interest in the cannabinoid (CBs) as a medicine, in the last two decades, cannabinoids have been extensively studied for their anti-cancer effects in various models of cancers including NHL, and have demonstrated promising effects against tumor growth, angiogenesis and metastasis. However, the anti-cancer effects of cannabinoids have never been studied in canine lymphoma and there is very limited literature available on the canine endocannabinoid system. Finding this wide-open area to study in canine lymphoma our aim of this research was to 1. Study the expression of cannabinoid receptors CB1 and CB2, 2. Analyze and compare the anti-cancer effects of cannabinoids in human and canine NHL cell lines and 3. To study the effect of cannabinoids in combination with traditional NLC drugs and compare it with the effect of CBs and NLC drugs alone.
To study the expression of cannabinoid receptors CB1 and CB2, canine B cell type (1771 and CLBL1) and T cell type (CL1) NHL cell lines, canine PMBCs and, human B cell type NHL cell line (Ramos) were used. Cells were cultured in RPMI, and receptor expression was studied using real-time PCR. Our results demonstrated positive expression of cannabinoid receptor CB1 and/or CB2 in both canine and human lymphoma cell lines, with a significantly higher expression of CB1 and CB2 receptors in canine and human B cell lymphoma cell lines, compared to activated PBMCs and canine CL-1 lymphoma cell line. For activated canine PBMCs our results show negative expression of the CB1 receptor gene but significantly higher expression of CB2 receptor gene compared to the canine T cell lymphoma cell line.
After establishing the expression of cannabinoid receptors, anti-cancer effects of cannabinoids [Endocannabinoids (AEA, 2AG), phytocannabinoids (CBD, THC) and synthetic cannabinoid (WIN)] on canine and human NHL cell lines were analyzed using MTT cell viability assay. Cells were treated at concentrations from 0.1µM to 50µM for 24 and 48 hours. Results of the cell viability assay demonstrate a dose-dependent decrease in cancer cell viability as compared to the control (cells treated with vehicle only) with AEA and CBD in both B and T cell type NHL cell lines. Treatment with WIN and THC showed dose-dependent decrease in cell viability in only B-cell NHL cell lines. 2-AG appeared to decrease cell viability in only lymphoma cell lines with higher CB2 receptor expression (Ramos and CLBL-1).
To further confirmed the anti-cancer effects of cannabinoids we selected canine B cell lymphoma cell line 1771 and exposed it to 0 (vehicle only) and 1µM and 50µM concentrations of cannabinoids for 24 h and protein was extracted. Markers of oxidative stress, mitochondrial function and apoptosis analyzed using biochemical spectrophotometric and fluorometric analysis. Results of the biochemical analysis revealed a cannabinoid-induced increase in markers of oxidative stress and apoptosis and a decrease in markers of mitochondrial functions in cells treated with cannabinoids (AEA, CBD, THC and WIN) as compared to the control.
To study the effect of cannabinoids in combination with traditional NHL chemotherapeutic drugs (NLC drugs), canine 1771 lymphoma cells were treated with CBs (AEA, CBD and WIN) and NLC drugs (DOX, CYC, VIN, LOM and PRD) alone and combinations. The cytotoxicity of each drug alone and combinations was analyzed by MTT assay and combination effect was analyzed using combinational index (CI) analysis. Our results demonstrated that the cytotoxic effects of all traditional NHL chemotherapy drugs were synergistically enhanced (interaction with CI <1) by each of the three cannabinoids when added to 1771 canine malignant B type NHL cells.
Taken together, these studies show the anti-cancer potential of cannabinoids against both canine and human NHL and provides a resource for developing therapeutics and testing safety prior to initiating canine and human studies
The Role of gyrA, Efflux Pump and Integrons in Mediating the Emergence of Multi-Drug Resistance among Canine and Feline Pathogenic Clinical Escherichia coli
No full textA series of experiments was performed to elucidate the emergence of fluoroquinolone (FQ)/multi-drug resistance (MDR) and the contribution of selected mechanisms of resistance to MDR (i.e. mutations in gyrA, efflux pump, and the integrons) in canine and feline pathogenic Escherichia coli. E. coli isolates (n= 377) were collected from dogs or cats with spontaneous infection between May and September 2005 for phenotypic (i.e. E-test®) and genotypic (i.e PFGE) characterization. Of isolates expressing resistance to any drug, two isolates expressed single drug resistance (SDR) only to enrofloxacin. The remaining 109 isolates expressing resistance to enrofloxacin also expressed MDR, with resistance to all 7 drugs (Z phenotype) representing the largest proportion (18.3%; 20/109). The drugs most commonly involved in MDR phenotypes (n=109) were amoxicillin (96.3 %; 105/109), amoxicillin-clavulanic acid (85%; 93/109)
and enrofloxcin (61.5%; 67/109). Genotypically, isolates were extensively diverse, regardless of resistance phenotype, and phenotypes and genotypes were not related.
For the first time, a FRET PCR was developed to identify enrofloxacin-resistance in clinical E. coli isolates that carry mutations in codon 83 and 87 of gyrA. The assay identified as few as four genome copies per reaction from culture and 19 genome copies in urine with a very short time (1-2 hrs). For the 70 isolates tested, the sensitivity of the test was 87.5% (95% CI = 75% to 95.3%) (n=42/48) whereas specificity was 100% (95% CI = 87.3% to 100%) (n=22/22). MICs for E. coli isolates (n= 536) were determined for enrofloxacin and five other drug classes using broth micro-dilution. FQ resistance was significantly associated with the MDR phenotype compared to non FQ-R isolates. The results suggest that the double mutation in gyrA confers high level of resistance to the majority of FQ-R isolates. Furthermore, the impact of an efflux pump was studied. Blocking the action of the AcrAB efflux pump (i) decrease the intrinsic level of the MICs to FQ in susceptible isolates, (ii) decrease the MICs below the susceptible break point for FQ-R isolates even with single mutation in gyrA, (iii) decrease the magnitude of resistance in highly resistance isolates in the presence of double mutations in gyrA (IV) decrease the MICs below the susceptible break point for some of the highly FQ-R isolates without gyrA mutations, and (V) decrease the resistance to structurally unrelated drugs, thus reducing the incidence of MDR. Integrons of Class I and 2 were identified in 27% of the isolates; thus only 2.4% of the isolates carried Class 2 integrons. All integron positive isolates were MDR, compared to 56.6% of integron negative isolates. Resistance resolved in the 3 MDR integron positive isolates subjected to plasmid curing (using 10 % SDS). This is the first report of class 2 integrons in E. coli from companion animals in US
Effect of tympanic cavity evacuation and flushing on microbial isolates during total ear canal ablation with lateral bulla osteotomy in dogs.
No full textOBJECTIVE
To evaluate differences in bacterial numbers, identity, and susceptibility in samples obtained from the tympanic cavity on entry (preflush) and after evacuation and lavage (postflush) and assess perioperative and empiric antimicrobial selection in dogs that underwent total ear canal ablation (TECA) with lateral bulla osteotomy (LBO) or reoperation LBO.
DESIGN
Prospective clinical study.
ANIMALS
34 dogs.
PROCEDURE
TECA with LBO or reoperation LBO was performed on 47 ears. Pre- and postflush aerobic and anaerobic samples were obtained from the tympanic cavity. Isolates and antimicrobial susceptibility patterns were compared.
RESULTS
Different isolates (31/44 [70%] ears) and susceptibility patterns of isolate pairs (6/44 [14%] ears) were detected in pre- and postflush samples from 84% of ears. Evacuation and lavage of the tympanic cavity decreased the number of bacterial isolates by 33%. In 26% of ears, bacteria were isolated from post-flush samples but not preflush samples. Only 26% of isolates tested were susceptible to cefazolin. At least 1 isolate from 53% of dogs that received empirically chosen antimicrobials postoperatively was resistant to the selected drugs. Anaerobic bacteria were recovered from 6 ears.
CONCLUSIONS AND CLINICAL RELEVANCE
Accurate microbiologic assessment of the tympanic cavity should be the basis for selection of antimicrobials in dogs undergoing TECA with LBO. Bacteria remain in the tympanic cavity after evacuation and lavage. Cefazolin was a poor choice for dogs that underwent TECA with LBO, as judged on the basis of culture and susceptibility testing results
Canine and Feline Differences in the Cytochrome P450 Transcriptome and Drug Metabolism
No full textCytochrome P450 (CYP) is an important enzyme superfamily, estimated to metabolize 70-90% of pharmaceuticals. Use of pharmaceuticals with at least 30% metabolism by CYP in humans require phenotyping to determine the CYP isoforms involved and the impact common polymorphisms may have. These same drugs are used off-label in canine and feline patients, yet knowledge regarding the CYP isoforms present in the liver and their enzymatic efficacy is unknown. Using human probes and substrates, differences in feline and canine CYP metabolism have been reported, and reflected in the limited pharmacokinetic (PK) studies of both species. The aim of this dissertation was to characterize canine and feline CYP transcriptome in canine and feline, compare and contrast the predicted hepatic clearance (CLhep) between the two species, and carry out reaction phenotyping of selected pharmaceuticals in canine recombinant CYP (rCYP). The first study determined the physiologic expression of CYP mRNA transcripts in whole blood, kidney, duodenum, liver and lung in healthy, adult male (n=4) and female (n=4) beagles via RNA-sequencing (RNA-seq). A total of 45 canine CYPs were identified, with liver, duodenum and lung expressing a high number of xenobiotic metabolizing CYPs, and expressing prominent endogenous metabolizing CYPs expression present in blood and kidney. In the second study, transcriptomes from the 99 Lives Cat Genome Sequencing Initiative databank combined with experimentally acquired whole transcriptome sequencing of healthy, adult male (n=2) and female (n=2) domestic felines was used to characterize CYP expression across a wide variety of tissues. A total of 20 tissues were analyzed and 47 CYP isoforms identified. Depending on the tissue, 9 to 33 CYP isoform transcripts were expressed. This study was the first to describe feline CYP transcriptome across a wide variety of tissues. Based on the differences in the transcriptome between the two species, the third study compared canine and feline CYP metabolism via in vitro liver microsomes. In canine liver microsomes, 3/30 substrates did not have quantifiable intrinsic clearance (CLint), while midazolam and amitriptyline CLint was too rapid for accurate determination. A predicted hepatic clearance (CLhep) was calculated for 29/30 substrates in feline microsomes. Overall, canine CLhep was faster compared to the feline, with fold differences ranging from 2 to 20 fold. A comparison between the well-stirred (CLhep,ws) and parallel tube model (CLhep,pt) indicates that the CLhep,pt model reports a slightly higher CLhep in both species. With evidence of the variation between the species, reaction phenotyping was applied to identify the CYP isoform pattern for targeted substrates. While the recombinant CYP (rCYP) isoforms are routinely used to screen novel human pharmaceuticals prior to approval, whether the canine isoforms metabolize these drugs in the same pattern is unknown. Utilizing an rCYP metabolic stability assay, 22 drugs used in veterinary medicine were phenotyped using canine rCYP1A1, 1A2, 2B6, 2C21, 2C41, 2D15, 3A12, and 3A26. Four of the 22 substrates required a two or four-fold rCYP dilution in order to achieve the three time points necessary to calculate the CLrCYP. The tricyclic antidepressants, amitriptyline and clomipramine, required a two or four-fold dilution of both rCYP2C41 and rCYP2D15. An isoform reported in only 11% of tested beagles, rCYP2C41, was involved in the metabolism of 9/22 substrates. The contribution of rCYP2B11 in canine drug metabolism altered the rCYP metabolism pattern for 8/22 substrates compared to the CYP metabolism pattern reported for humans. This body of research identified differences in the CYP transcriptome and CYP substrate depletion profile between the two species that suggests the need for species-specific pharmacokinetic studies as a basis for design of dosing regimens. In addition, canine CYP2B11 metabolism does not follow the reported human profile, highlighting the need for canine- and feline-specific reaction phenotyping
Pharmacokinetics of intraperitoneal infusion of lidocaine in horses
No full textThe objective of this study was to describe the pharmacokinetics of intraperitoneal (IP) lidocaine in horses (30mg/kg). The study was designed as double blinded cross-over, placebo controlled clinical trial, with a 2 weeks washout period. All horses were part of the research herd of the Auburn University Large Animal Teaching Hospital. Four healthy adult, mixed breed horses, 8 to 15 years of age, that weighed between 490 and 570 kg were randomly assigned to receive either placebo or lidocaine first.
A solution of 5 liters of balanced electrolyte solution with or without 2% lidocaine at a dose of 30 mg/kg was injected IP over 20 minutes. Horses were monitored for 24 hours after IP infusion for signs of toxicity. Blood was collected at 0, 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360, 480, and 1440 minutes after infusion. Samples of peritoneal fluid (PF) were obtained at minutes 0, 60, 120, 360 and 1440 minutes. Lidocaine and its active metabolite monoethylglycinexylidide (MEGX) were quantified in plasma and PF using high performance liquid chromatography. Time versus concentration data were subjected to non-compartmental analysis.
Peak plasma (Cmax) lidocaine and MEGX concentrations were 2.82 ± 0.84μg/ml and 5.58 ± 3.78 μg/ml, respectively; time to maximum concentration was 75 ± 71 min and 93 ± 98 min respectively. Plasma lidocaine concentration remained above 1 μg/ml for 2 hours and declined to non-quantifiable concentration (< 0.2 μg/ml) by 8 hours after infusion. For IP, Cmax for lidocaine and MEGX were 2.82 ± 0.84 and 5.58 ± 3.78 μg/ml, respectively. Clinical signs indicative of lidocaine adversity occurred in one horse after IP administration of lidocaine; this horse recovered completely in 45 minutes without intervention. Further studies are indicated to
` III
establish an IP dose of lidocaine necessary to achieve its target effects without causing adverse effects
Pharmacokinetics of albuterol and butorphanol administered intravenously and via a buccal patch
No full textConventional routes of drug administration have several disadvantages. The rate and extent of absorption can vary greatly depending on the drug, its formulation, the presence or absence of food, drug interactions, and the pH of gastrointestinal fluids. Extensive first-pass metabolism can greatly reduce the absorption of many drugs. Better dosage forms or drug delivery mechanisms could minimize some of these problems.
The pharmaceutical industry has recognized the need for, and has developed many new, novel drug delivery systems. Drugs that previously experienced diminished effective concentrations due to the first-pass effect may now be given by a novel route. The dosing frequency of many drugs may be reduced when administered by a novel route or site. Transmucosal drug delivery (TMDD) via the buccal mucosa is one site that is suited to rapid drug absorption and systemic delivery. Drugs selected for TMDD must have physiochemical properties that will allow them to penetrate the mucosa and produce therapeutic blood concentrations. This study utilized a buccal patch less than 1.5 cm in length to deliver albuterol and butorphanol-two drugs with dissimilar physiochemical properties.
The purpose of this study was to establish pharmacokinetic parameters and the bioavailability of albuterol and butorphanol when administered intravenously and buccally. Three dogs weighing at least 20 kg were studied using a randomized crossover design, each receiving albuterol and butorphanol by buccal and intravenous administration. Blood samples were collected and analyzed using ELISA. Values for pharmacokinetic parameters were analyzed using compartmental and non-compartmental models.
For albuterol, extrapolated Cmax and Co after buccal and IV administration were 10.28 �� 2.77 and 57.74 �� 9.04 ng/ml, respectively. Volume of distribution at steady state (Vss) was 2.13 �� 1.30 L/kg and Cl was 4.73 �� 3.91 ml/min/kg. A significant difference existed between the disappearance rate constant of buccal and intravenous albuterol administration. The disappearance half-lives of buccal and IV albuterol were 160.96 �� 24.19 and 364.20 �� 115.20 min, respectively. The bioavailability of buccally administered albuterol was 35%.
Maximal concentration (Cmax) and Co after buccal and IV butorphanol administration were 6.66 �� 1.65 and 8.24 �� 5.55 ng/ml, respectively. Volume of distribution at steady state (Vss) was 27.58 �� 10.14 L/kg and Cl was 137.87 �� 19.55 ml/min/kg. The half-life of buccally administered butorphanol was 259.15 �� 33.12 min and the half-life of IV butorphanol was 172.12 �� 94.95 min. The bioavailability of buccally administered butorphanol was 606%.
The buccal patch used in this study achieved systemic concentrations for both albuterol and butorphanol. Further studies are needed to determine if therapeutic drug concentrations can be achieved with the buccal patch and if the patch can result in clinical efficacy
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