Training Surgical Residents Utilizing an Animal Shelter Fracture Program.

Working relationships between veterinary medical teaching hospitals, animal shelters, and rescue groups are one way to increase veterinary students' and residents' hands-on training. The goal of this study is to describe the use of a shelter fracture program to improve the surgical skills of surgical residents. In this program, the participating shelter and rescue organizations electronically submit cases. Following evaluation of radiographs and case approval by the orthopedic faculty, the case is scheduled for a physical evaluation. A resident takes primary surgical care together with a fourth-year student rotating through the orthopedic surgery service to ensure the proper pre-, peri-, and post-operative standard of care. All care is overseen by the orthopedic faculty. A veterinary student-run fracture foster program allows students to gain additional experience in the pre-, peri-, and post-operative care of shelter animals. The total number of shelter animals treated during a 9-year period was 373, with a mean annual case load of 41.1 cases (± 10.3). During the same time period, a total of 435 client-owned cases underwent surgical fracture treatment, with a mean annual case load of 48 cases (± 11.7). Surgical resident and student surveys show that this program contributes to their knowledge, skills, and confidence in treating fracture patients. A successful cooperative program provides advanced surgical fracture treatment of shelter animals, improving animals' quality of life as well as surgical residents' and veterinary students' skills training.

Correction to: Assessment of burnout in veterinary medical students using the Maslach Burnout Inventory-Educational Survey: a survey during two semesters.

An amendment to this paper has been published and can be accessed via the original article.

An Inter-Institutional Collaboration to "Make Teaching Matter": The Teaching Academy of the Consortium of West Region Colleges of Veterinary Medicine.

Veterinary medical education is a relatively small community with limited numbers of institutions, people, and resources widely dispersed geographically. The problems faced, however, are large-and not very different from the problems faced by (human) medical education. As part of an effort to share resources and build a community of practice around common issues, five colleges in the westernmost region of the United States came together to form a regional inter-institutional consortium. This article describes the processes by which the consortium was formed and the initiation of its first collaborative endeavor, an inter-institutional medical/biomedical teaching academy (the Regional Teaching Academy, or RTA). We report outcomes, including the successful launch of three RTA initiatives, and the strategies that have been considered key to the academy's success. These include strong support from the consortium deans, including an ongoing financial commitment, a dedicated part-time Executive Coordinator, regular face-to-face meetings that supplement virtual meetings, an organization-wide biennial conference, an effective organizational structure, and a core group of dedicated leaders and RTA Fellows. The western consortium and RTA share these processes, insights, and outcomes to provide a model upon which other colleges of veterinary medicine can build to further leverage inter-institutional collaboration.

Collaborative Development of a Shared Framework for Competency-Based Veterinary Education.

Competency-based medical education is an educational innovation implemented in health professions worldwide as a means to ensure graduates meet patient and societal needs. The focus on student-centered education and programmatic outcomes offers a series of benefits to learners, institutions and society. However, efforts to establish a shared, comprehensive competency-based framework in veterinary education have lagged. This article reports on the development and outcome of a competency-based veterinary education (CBVE) framework created through multi-institutional collaboration with international input from veterinary educators and veterinary educational leaders. The CBVE Framework is designed to reflect the competencies expected of new graduates from member institutions of the Association of American Veterinary Medical Colleges (AAVMC). The CBVE Framework consists of nine domains of competence and 32 competencies, each supplemented with illustrative sub-competencies to guide veterinary schools in implementing competency-based education in their local context. The nine domains of competence are: clinical reasoning and decision-making; individual animal care and management; animal population care and management; public health; communication; collaboration; professionalism and professional identity; financial and practice management; and scholarship. Developed through diverse input to facilitate broad adoption, the CBVE Framework provides the foundation for competency-based curricula and outcomes assessment in veterinary education internationally. We believe that other groups seeking to design a collective product for broad adoption might find useful the methods used to develop the CBVE Framework, including establishing expertise diversity within a small-to-medium size working group, soliciting progressive input and feedback from stakeholders, and engaging in consensus building and critical reflection throughout the development process.

Collaborative Development of Core Entrustable Professional Activities for Veterinary Education.

Entrustable professional activities (EPAs) have been proposed as a practical framework for the implementation of competency-based education. As veterinary education moves toward a competency-based approach, core EPAs provide a context for assessment of workplace activities. This article reports on the development of eight core clinical EPAs for veterinary education created through multi-institutional collaboration, with international input from veterinary educators and veterinary educational leaders. These core EPAs are intended as minimal expectations for clinical activities that should be assessed for every graduate of Association of American Veterinary Medical Colleges member institutions. Adoption of the core EPAs and the associated Competency-Based Veterinary Education (CBVE) framework by veterinary schools is intended to promote Day One graduate competence and thereby enhance patient care and client service.

Correction to: Assessment of burnout in veterinary medical students using the Maslach burnout inventory-educational survey: a survey during two semesters.

Following publication of the original article [1], we've been notified by an author that they have published their manuscript without seeking permission for the survey that was included in one of their tables (Table 1).

Development of core entrustable professional activities linked to a competency-based veterinary education framework.

Purpose: Despite the adoption of competency-based education in some veterinary schools over the past 15 years, only recently has a concerted effort been directed toward this in veterinary education internationally.Methods: In 2015, educational leaders from the Association of American Veterinary Medical Colleges (AAVMC) member schools came together with a strong call to action to create shared tools for clinical competency assessment.Results: This resulted in the formation of the AAVMC Competency-Based Veterinary Education (CBVE) Working Group, which then embarked on the creation of a shared competency framework and the development of eight core entrustable professional activities (EPAs) linked to this framework.Conclusions: This paper will report on the development of these EPAs and their integration with the concurrently-developed CBVE Framework.

Is a veterinary student's performance on multiple-mini interviews affected by personality preferences?

OBJECTIVES: The objectives of this study were to evaluate the association between a student's Myers-Briggs Type Indicator (MBTI) preference pairs and resulting types and his or her multiple-mini interview (MMI) scores upon admission, and to determine the proportions of types among veterinary classes over five years. METHODS: A cross-sectional study was conducted for data collected from 706 students admitted into the University of California Davis School of Veterinary Medicine (UCDSVM) program beginning in the fall of 2013 and ending in the fall of 2018. Data consisted of a candidate's MBTI preference pairs and types which were collected during the first week of enrollment and multiple-mini interview scores from his or her admission data. RESULTS: A total of 706 students from 5 classes completed the MBTI survey. Multivariate analysis showed no significant association between the MBTI preference pairs of extroversion and introversion (F(1, 697) = 3.30, p=0.0959), sensing and intuition (F(1, 697) = 0.40, p=0.4395), thinking and feeling (F(1, 697) = 3.59, p=0.0591), or judging and perceiving (F(1, 697) = 0.38, p = 0.5657) and MMI score. Analysis showed no trends (χ2 (60, N=706) =76.51, p=0.074) in the student's MBTI types over the 5-year period. CONCLUSIONS: The MMI score of a candidate admitted into the UCDSVM is unlikely to be affected by personality preferences. Therefore, it is unlikely that multiple-mini interview scores included in the admission process will affect the personality diversity of candidates admitted into a veterinary class.

Assessment of Depression and Health-Related Quality of Life in Veterinary Medical Students: Use of the 2-Item Primary Care Evaluation of Mental Disorders Questionnaire (PRIME-MD PHQ) and the 8-Item Short Form-8 Survey (SF-8).

Depression and health-related quality of life (HRQOL) are major concerns affecting veterinary students' well-being. Shorter versions of instruments to assess depression and HRQOL are timesaving and preferable. To the authors' knowledge there are no studies available that assess HRQOL in veterinary students. The objectives of this study were to screen veterinary students for depression during two semesters using a 2-item Primary Care Evaluation of Mental Disorders Procedure Health Questionnaire (PRIME-MD PHQ), and to assess HRQOL over two semesters using the Optum Short Form-8 (SF-8) Health Survey. A cohort of 273 students from two classes were invited to complete the PRIME-MD PHQ and the SF-8 survey during the fall semester of their first year, and again in the spring semester of the second year. Descriptive statistics, factor analysis, multiple regression, and logistic regression were used to perform data analysis. The proportion of students with symptoms of depression was high, ranging from 37.4% to 56.8% between the two classes. The SF-8 survey indicated a mental component summary (MCS) score of <50, indicating poor mental health for both classes, whereas the physical component summary (PCS) was >50, suggesting good physical health. Female students (p =.043) had low MCS scores compared to males. Students from both classes had lower MCS scores in spring compared to fall (p =.019). The PRIME-MD PHQ and the SF-8 were acceptable instruments for assessing depression and HRQOL in veterinary students, respectively.

Hemodynamic effects of dexmedetomidine, with and without MK-467, following intramuscular administration in cats anesthetized with isoflurane.

OBJECTIVE: To characterize the hemodynamic effects of dexmedetomidine, with or without MK-467, following intramuscular (IM) administration in cats. STUDY DESIGN: Randomized, crossover, experimental study. ANIMALS: Six healthy adult male castrated purpose-bred cats. METHODS: Cats were anesthetized with isoflurane in oxygen and instrumented. Cats were administered dexmedetomidine (25 µg kg-1), with (DM) or without (D) MK-467 (600 µg kg-1), IM in the epaxial muscles. Cardiovascular variables, respiratory variables, temperature, and arterial and mixed-venous pH, blood gases and electrolytes were measured prior to drug administration and at various time points for 6 hours thereafter, during anesthesia with isoflurane. Additional variables were calculated from the measurements, using standard equations. Results were analyzed with a two-way repeated-measures analysis of variance, followed by Dunnett's and paired t tests where appropriate. RESULTS: Dexmedetomidine resulted in a significant decrease in cardiac index (CI) and significant increases in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI). The addition of MK-467 failed to prevent most of the early cardiovascular effects of dexmedetomidine, but the duration of systemic vasoconstriction was shorter and CI did not decrease. The lowest and highest post-treatment values in each treatment were 0.1 ± 0.03 and 0.13 ± 0.03 L minute-1 BW-0.67 (D) versus 0.14 ± 0.01 and 0.19 ± 0.03 L minute-1 BW-0.67 (DM) for CI, 87 ± 13 and 181 ± 21 mmHg (D) versus 70 ± 11 and 153 ± 18 mmHg (DM) for MAP and 58,948 ± 17,754 and 119,432 ± 40,423 dynes second cm-5 BW-0.67 (D) versus 25,870 ± 3782 and 76,498 ± 17,258 dynes second cm-5 BW-0.67 (DM) for SVRI, respectively. CONCLUSION AND CLINICAL RELEVANCE: IM coadministration of MK-467 and dexmedetomidine in isoflurane-anesthetized cats shortened dexmedetomidine-induced cardiovascular effects. This drug combination may be useful in cats in which longer-lasting hypertension and hemodynamic depression is of concern.

Approaches and Study Skills of Veterinary Medical Students: Effects of a Curricular Revision.

The objective of this study was to determine if a revised, recently implemented curriculum, embracing an integrated block design with a focus on student-centered, inquiry-based learning, had a different effect on veterinary medical students' approaches to studying than the previous curriculum. A total of 577 students completed a questionnaire consisting of the short version of the Approaches and Study Skills Inventory for Students (ASSIST). It included questions relating to conceptions about learning, approaches to studying, and preferences for different types of courses and teaching. In addition, students were asked to respond to general questions regarding the design of the revised curriculum. The scores for the deep and strategic learning approaches were higher for students studying under the previous curriculum compared to the revised curriculum, despite the fact that the revised curriculum was specifically designed to foster deep learning. The scores for the surface learning approach were lower in the students studying the revised curriculum compared to students studying under the previous curriculum. We identified the following factors affecting student learning: alteration of learning activities, such as problem-based learning, from the recommended models; a lack of instructor support for the revised curriculum; assessments that were not aligned to encourage critical thinking; and directed self-learning activities that were too comprehensive to complete in the allotted time. The results of this study can be used to improve the implementation of student-centered and inquiry-based curricula by identifying potential problems that could prevent a deep learning approach in veterinary medical students.

Curricular Revision and Reform: The Process, What Was Important, and Lessons Learned.

Beginning in 2005, the Doctor of Veterinary Medicine program at the University of California underwent major curricular review and reform. To provide information for others that follow, we have documented our process and commented on factors that were critical to success, as well as factors we found surprising, difficult, or problematic. The review and reform were initiated by the Executive Committee, who led the process and commissioned the committees. The planning stage took 6 years and involved four faculty committees, while the implementation stage took 5 years and was led by the Curriculum Committee. We are now in year 2 of the institutionalizing stage and no longer refer to our reform as the "new curriculum." The change was driven by a desire to improve the curriculum and the learning environment of the students by aligning the delivery of information with current teaching methodologies and implementing adult learning strategies. We moved from a department- and discipline-based curriculum to a school-wide integrated block curriculum that emphasized student-centered, inquiry-based learning. A limit was placed on in-class time to allow students to apply classroom knowledge by solving problems and cases. We found the journey long and arduous, requiring tremendous commitment and effort. In the change process, we learned the importance of adequate planning, leadership, communication, and a reward structure for those doing the "heavy lifting." Specific to our curricular design, we learned the importance of the block leader role, of setting clear expectations for students, and of partnering with students on the journey.

Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats.

OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. STUDY DESIGN: Prospective randomized crossover experimental study. ANIMALS: A total of eight healthy adult male castrated cats aged 1-2 years. METHODS: Cats were administered dexmedetomidine (25 µg kg-1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 µg kg-1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 µg kg-1) IM with 300, 600 or 1200 µg kg-1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. RESULTS: A one-compartment model best fitted the time-plasma dexmedetomidine concentration data in cats administered D25IM, and the time-plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time-plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time-plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time-concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792-1890) and 924 (596-1649) ng minute mL-1, 4.4 (0.4-15.7) and 2.3 (0.2-8.0) minutes, 10.2 (4.8-16.9) and 17.8 (15.8-73.5) ng mL-1, 17.8 (2.6-44.9) and 5.2 (1.2-15.1) minutes and 62 (52-139) and 50 (31-125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.

Spatial and Visual Reasoning: Do These Abilities Improve in First-Year Veterinary Medical Students Exposed to an Integrated Curriculum?

Spatial visualization ability refers to the human cognitive ability to form, retrieve, and manipulate mental models of spatial nature. Visual reasoning ability has been linked to spatial ability. There is currently limited information about how entry-level spatial and visual reasoning abilities may predict veterinary anatomy performance or may be enhanced with progression through the veterinary anatomy content in an integrated curriculum. The present study made use of two tests that measure spatial ability and one test that measures visual reasoning ability in veterinary students: Guay's Visualization of Views Test, adapted version (GVVT), the Mental Rotations Test (MRT), and Raven's Advanced Progressive Matrices Test, short form (RavenT). The tests were given to the entering class of veterinary students during their orientation week and at week 32 in the veterinary medical curriculum. Mean score on the MRT significantly increased from 15.2 to 20.1, and on the RavenT significantly increased from 7.5 to 8.8. When females only were evaluated, results were similar to the total class outcome; however, all three tests showed significant increases in mean scores. A positive correlation between the pre- and post-test scores was found for all three tests. The present results should be considered preliminary at best for associating anatomic learning in an integrated curriculum with spatial and visual reasoning abilities. Other components of the curriculum, for instance histology or physiology, could also influence the improved spatial visualization and visual reasoning test scores at week 32.

Cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous administration in cats.

OBJECTIVE: To characterize the cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous (IV) administration in cats. STUDY DESIGN: Prospective Latin square experimental study. ANIMALS: Six healthy adult purpose-bred cats. METHODS: Cats were anesthetized with desflurane in oxygen for instrumentation with a carotid artery catheter and a thermodilution catheter in the pulmonary artery. One hour after discontinuation of desflurane, cats were administered dexmedetomidine (25 µg kg-1), MK-467 (600 µg kg-1), or dexmedetomidine (25 µg kg-1) and MK-467 (600 µg kg-1). All treatments were administered IV as a bolus. Cardiovascular variables were measured prior to drug administration and for 8 hours thereafter. Only data from the dexmedetomidine and dexmedetomidine-MK-467 treatments were analyzed. RESULTS: Dexmedetomidine produced significant decreases in heart rate, cardiac index and right ventricular stroke work index, and significant increases in arterial blood pressure, central venous pressure, pulmonary artery pressure and systemic vascular resistance index. Dexmedetomidine combined with MK-467 resulted in significant but transient decrease in blood pressure and right ventricular stroke work index. CONCLUSION AND CLINICAL RELEVANCE: Following IV co-administration, MK-467 effectively attenuated dexmedetomidine-induced cardiovascular effects in cats. The drug combination resulted in transient reduction in arterial blood pressure, without causing hypotension.

The State of Veterinary Dental Education in North America, Canada, and the Caribbean: A Descriptive Study.

Dental disease is important in the population of pets seen by veterinarians. Knowledge and skills related to oral disease and dentistry are critical entry-level skills expected of graduating veterinarians. A descriptive survey on the state of veterinary dental education was sent to respondents from 35 veterinary schools in the United States, Canada, and the Caribbean. Using the online SurveyMonkey application, respondents answered up to 26 questions. Questions were primarily designed to determine the breadth and depth of veterinary dental education from didactic instruction in years 1-3 to the clinical year programs. There was an excellent response to the survey with 86% compliance. Learning opportunities for veterinary students in years 1-3 in both the lecture and laboratory environments were limited, as were the experiences in the clinical year 4, which were divided between community-type practices and veterinary dentistry and oral surgery services. The former provided more hands-on clinical experience, including tooth extraction, while the latter focused on dental charting and periodontal debridement. Data on degrees and certifications of faculty revealed only 12 programs with board-certified veterinary dentists. Of these, seven veterinary schools had residency programs in veterinary dentistry at the time of the survey. Data from this study demonstrate the lack of curricular time dedicated to dental content in the veterinary schools participating in the survey, thereby suggesting the need for veterinary schools to address the issue of veterinary dental education. By graduation, new veterinarians should have acquired the needed knowledge and skills to meet both societal demands and professional expectations.

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

OBJECTIVE: To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. STUDY DESIGN: Randomized crossover study. ANIMALS: Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. METHODS: Morphine sulfate (0.2 mg kg-1 IV or 0.5 mg kg-1 buccal), methadone hydrochloride (0.3 mg kg-1 IV or 0.75 mg kg-1 buccal), hydromorphone hydrochloride (0.1 mg kg-1 IV or 0.25 mg kg-1 buccal) or oxymorphone hydrochloride (0.1 mg kg-1 IV or 0.25 mg kg-1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. RESULTS: Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. CONCLUSION AND CLINICAL RELEVANCE: At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients.

Assessment of burnout in veterinary medical students using the Maslach Burnout Inventory-Educational Survey: a survey during two semesters.

BACKGROUND: Burnout among veterinary students can result from known stressors in the absence of a support system. The objectives of this study were to evaluate use of the Maslach Burnout Inventory-Educator Survey (MBI-ES) to assess burnout in veterinary students and evaluate the factors that predict the MBI-ES scores. METHODS: The MBI-ES was administered to first (Class of 2016) and second year (Class of 2015) veterinary medical students during the 2012-2013 academic year in the fall and spring semesters. Factor analysis and test reliability for the survey were determined. Mean scores for the subscales determining burnout namely emotional exhaustion (EE), depersonalization (DP) and lack of personal accomplishment (PA) were calculated for both classes in the 2 semesters. Multiple regression analysis was performed to evaluate other factors that predict the MBI-ES scores. RESULTS: A non-probability sampling method was implemented consisting of a voluntary sample of 170 and 123 students in the fall and spring semesters, respectively. Scores for EE, DP and PA were not different between the 2 classes within the same semester. Mean ± SD scores for EE, DP and PA for the fall semester were 22.9 ± 9.6, 5.0 ± 4.8 and 32.3 ± 6.7, respectively. Mean ± SD scores for EE, DP and PA the spring semester were 27.8 ± 10.7, 6.5 ± 6.1and 31.7 ± 6.8, respectively. The EE score was higher in spring compared to fall while DP and PA scores were not different between the 2 semesters. Living arrangements specifically as to whether or not a student lived with another veterinary medical students was the only variable significantly associated with the MBI-ES scores. Students in this study had moderate levels of burnout based on the MBI-ES scores. CONCLUSIONS: The MBI-ES was an acceptable instrument for assessing burnout in veterinary medical students. The EE scores were higher in the spring semester as compared to the fall semester. Thus students in the first and second years of veterinary school under the current curriculum experience the greatest levels of emotional exhaustion during the spring semester. This has administrative implications for the school, when considering the allocation and use of resources for student support systems during each semester.

Pharmacokinetics of dexmedetomidine after intravenous administration of a bolus to cats.

OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine after IV administration of a bolus to conscious healthy cats. ANIMALS: 5 healthy adult spayed female cats. PROCEDURES: Dexmedetomidine was administered IV as a bolus at 3 doses (5, 20, or 50 µg/kg) on separate days in a random order. Blood samples were collected immediately before and at various times for 8 hours after drug administration. Plasma dexmedetomidine concentrations were determined with liquid chromatography-mass spectrometry. Compartment models were fitted to the concentration-time data by means of nonlinear regression. RESULTS: A 2-compartment model best fit the concentration-time data after administration of 5 µg/kg, whereas a 3-compartment model best fit the data after administration of 20 and 50 µg/kg. The median volume of distribution at steady-state and terminal half-life were 371 mL/kg (range, 266 to 435 mL/kg) and 31.8 minutes (range, 30.3 to 39.7 minutes), respectively, after administration of 5 µg/kg; 545 mL/kg (range, 445 to 998 mL/kg) and 56.3 minutes (range, 39.3 to 68.9 minutes), respectively, after administration of 20 µg/kg; and 750 mL/kg (range, 514 to 938 mL/kg) and 75.3 minutes (range, 52.2 to 223.3 minutes), respectively, after administration of 50 µg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics of dexmedetomidine was characterized by a small volume of distribution and moderate clearance and had minimal dose dependence within the range of doses evaluated. These data will help clinicians design dosing regimens once effective plasma concentrations are established.