About

Mark Papich is a faculty member associated with the College of Veterinary Medicine at NC State University. The page text does not provide specific details about his research focus, background, or key contributions. Therefore, no detailed biography can be extracted from the provided content.

Research topics

• Pharmacology
• Medicine
• Internal medicine
• Microbiology
• Biology
• Veterinary medicine
• Gastroenterology
• Intensive care medicine
• Risk analysis (engineering)
• Anesthesia
• Bioinformatics
• Emergency medicine
• Business
• Family medicine

Selected publications

• Sustained elution of amikacin, clindamycin, and vancomycin from a biodegradable cross-linked dextran gel

  Scientific Reports · 2026-03-19

  articleOpen access

  Osteomyelitis, surgical site infections, implant infections, abscesses, and other localized infections can be difficult to treat due to poor vascularity, biofilm formation, and the presence of antibiotic-resistant bacteria. These infections result in significant morbidity and mortality in human and veterinary patients. Local delivery of high concentrations of antibiotics that are released over a prolonged period of time can overcome these issues, and avoid side effects of systemic antibiotics. In vitro release kinetics of amikacin, clindamycin, and vancomycin from a cross-linked dextran (CLD) gel were investigated. The hypothesis was that CLD gel containing vancomycin, amikacin, clindamycin or a combination of amikacin and clindamycin would elute concentrations above the MIC of common bacterial pathogens for 7 days in vitro. Elution kinetics of CLD gels impregnated with each antibiotic and control gel were tested an in vitro. Each gel was incubated with phosphate-buffered saline at 37 °C with agitation in triplicate. The media was changed every 24 h. Samples from the experimental and control gels were collected for a period of 16 days and antibiotic concentrations were determined. Mean antibiotic concentrations from CLD gel remained above the MIC for at least 7 days for each of the antibiotics investigated. Peak mean antibiotic concentrations occurred at 24 h. In sum, there is reliable elution over 7 days of amikacin, clindamycin and vancomycin from CLD gel at clinically relevant concentrations.

  PublisherOA PDFDOI

• Population Pharmacokinetics of Sildenafil in Dogs With Naturally Occurring Pulmonary Hypertension

  Journal of Veterinary Pharmacology and Therapeutics · 2026-02-24

  articleOpen accessSenior authorCorresponding

  The pharmacokinetics of sildenafil are ill-defined in dogs with naturally occurring pulmonary hypertension (PH). Because the plasma concentrations of sildenafil have not been reported for dogs with this disease, this study aimed to describe the population pharmacokinetics of sildenafil in a sample of dogs with PH. Twenty client-owned dogs with spontaneous PH associated with diverse comorbidities and receiving orally administered sildenafil were enrolled in a prospective, open-label, steady-state population pharmacokinetic study. Dogs underwent a sparse-sampling blood collection protocol after the morning dose of sildenafil. Plasma sildenafil concentrations were determined using high-pressure liquid chromatography and mass spectrometry. Population pharmacokinetic analysis with nonlinear mixed effects modeling was performed, and selected covariates were evaluated in the model. Sildenafil was rapidly absorbed (absorption half-life 1.1 h) but variable (CV 94%) and reached maximal plasma concentrations at 2.51 h. The estimated elimination half-life was 2.9 h. However, substantial individual variability in pharmacokinetics of sildenafil was evident, unexplained by the covariates examined, and attributed primarily to the high variability in absorption. This finding supports the need for a large-scale study to identify the source of this variability to better guide therapy in poor responders to initial therapy with this drug.

  PublisherDOI

• Ertapenem Pharmacokinetics in Equine Plasma and Synovial Fluid Following a Single Intravenous Dose

  Journal of Veterinary Pharmacology and Therapeutics · 2026-02-16

  articleOpen access

  This study describes the pharmacokinetics of ertapenem, a carbapenem antimicrobial that has not been previously studied in equids. Administered as a 30 mg/kg intravenous bolus to six healthy horses, serial blood and synovial samples were obtained over 8 h after administration. Pharmacokinetic analysis of plasma and synovial fluid was performed. In plasma, the AUC was 353.10 h × μg/mL (CV = 49.02%), Vss 79.34 mL/kg (CV = 22.85%), CL 84.96 mL/h/kg (CV = 31.31%) and t1/2 2.03 h (CV = 15.32%). In synovial fluid, the AUC was 524.10 h × μg/mL (CV = 16.03%), VD 206.32 mL/kg (CV = 30.55%), CL 57.24 mL/h/kg (CV = 16.03%) and t1/2 2.50 h (CV = 32.47%). Synovial fluid maintained higher concentrations of ertapenem for longer, although exhibited a lower maximum concentration compared to plasma. The six most common surgical site infection isolates at a tertiary care center in equine orthopedic cases, and their susceptibility to ertapenem were evaluated. The isolates identified were largely consistent with previous reports. The drug was well tolerated, although it caused transient soft feces. Carbapenems remain a protected class of antimicrobials which should be reserved for cases where culture and susceptibility results support their administration. This study helps inform appropriate dosage and dosing intervals.

  PublisherOA PDFDOI

• Pharmacokinetics of Diclazuril in the Plasma and Cerebrospinal Fluid of Healthy Adult Horses After a Single Oral Dose Administered as a Pelleted Topdressing

  Journal of Veterinary Pharmacology and Therapeutics · 2026-05-16

  article

  Equine protozoal myeloencephalitis can cause acute infections with rapid onset of neurologic signs, necessitating immediate empiric therapy with antiprotozoal medication. The objective of the study was to identify when concentrations of diclazuril reached the MIC of Sarcocystis neurona in CSF (1 ng/mL) of healthy adult horses after a single oral dose. Six healthy adult horses were used. Blood and CSF were collected from indwelling intravenous jugular catheters and intrathecal catheters in the lumbosacral space prior to drug administration and then at 1-, 4-, 8-, 12-, 16-, 24-, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h post-administration of a 1 mg/kg dose of pelleted diclazuril administered by mouth in 8 oz of sweet feed. Samples were centrifuged then plasma and CSF supernatant were separated and frozen at -80°C until analysis. Diclazuril concentrations were analyzed with a liquid chromatography-mass spectrometer assay developed specifically for this study. Plasma concentrations of diclazuril peaked at 48 h with a mean concentration of 395.6 ± 109.4 ng/mL. CSF concentrations of diclazuril peaked at 24 h (mean concentration 9.0 ± 5.4 ng/mL) but achieved the MIC of S. neurona 12 h after administration (mean concentration 2.6 ± 1.8 ng/mL) and remained above MIC for the duration of the sampling period. In conclusion, pelleted diclazuril at 1 mg/kg reaches concentrations in the CSF above the MIC for S. neurona in healthy horses 12 h after a single oral dose.

  PublisherDOI

• SHOULD EQUINE PRACTITIONERS STILL PRESCRIBE CHLORAMPHENICOL FOR TREATING HORSES?

  2026-02-09

  articleOpen access1st authorCorresponding

  Background: Clinical breakpoints for chloramphenicol are not currently available to test susceptibility of bacteria isolated from horses. Without these breakpoints, testing the susceptibility of bacterial isolates from horses cannot be performed properly Objective: Our objective was to develop antimicrobial susceptibility testing breakpoints for testing bacteria isolated from horses and determine if the use of chloramphenicol in horses can be justified. Study Design: Our design incorporated a search of the pharmacokinetic literature to identify pharmacokinetic data from horses and perform pharmacokinetic-pharmacodynamic (PK-PD) analysis on those data. We combined the analysis with minimal inhibitory concentration (MIC) data for bacteria that cause infections in horses. Methods: Dose-exposure data for oral administration of chloramphenicol to horses, along with the PK-PD index of unbound drug area under the concentration time curve in plasma over a 24-hr dosing period ( f AUC 24 ) divided by a bacterial minimal inhibitory concentration (MIC) was used to predict efficacy of chloramphenicol administered by the oral route to horses. Results: An analysis of multiple pharmacokinetic studies from oral administration of chloramphenicol to horses generated LS-mean values and associated variability for pharmacokinetic parameters. 10,000 Monte Carlo simulations were generated to determine the MIC at which 90% of the simulated population would achieve the PK-PD target. Main Limitations: This analysis was performed using published pharmacokinetic data and MIC values collected from a monitoring program. We cannot ensure that our analysis reflects the performance of chloramphenicol for treating a clinical infection. Conclusions: Based on this analysis, a suggested clinical breakpoint for susceptible pathogens is 0.5 µg/mL. This value is well below the range of Escherichia coli, Staphylococcus aureus, and Streptococcus equi (subspecies equi and zooepidemicus) chloramphenicol MIC values that are likely to be encountered in horses. Chloramphenicol is unlikely to be effective in the treatment of bacterial infections in horses.

  PublisherOA PDFDOI

• Proposed Meropenem Breakpoints for Interpretation of Antimicrobial Susceptibility Testing of Bacteria Isolated From Dogs

  Journal of Veterinary Pharmacology and Therapeutics · 2026-03-17

  articleOpen access1st authorCorresponding

  Meropenem is a carbapenem antibiotic used infrequently in veterinary medicine. However, antimicrobial susceptibility testing standards are needed to monitor for resistance caused by carbapenem resistant Enterobacterales (CRE). The Clinical and Laboratory Standards Institute (CLSI) does not have veterinary-specific carbapenem breakpoints for testing bacteria isolated from animals. Our objective was to correct this deficiency and propose clinical antimicrobial susceptibility testing breakpoints for consideration by clinical laboratories, standard-setting organizations, and for monitoring and surveillance programs. We collected pharmacokinetic data from published studies, which were entered into a forecasting program to perform 10,000 Monte Carlo Simulation using a range of dosages considered for administration of meropenem to dogs. Our target for the simulations was a 90% Probability of Target Attainment (PTA) to reach a time-above-MIC for the unbound fraction of the drug (f T > MIC) for at least 40% of the dosing interval. Our results showed that this target can be met for a MIC of ≤ 1 μg/mL (Enterobacterales) with a dose of 20-30 mg/kg IV every 8 h or 10 mg/kg every 6 h. For a one-step higher dilution of ≤ 2 μg/mL (Pseudomonas aeruginosa), a dose of 20-30 mg/kg every 6 h is needed. Therefore, we propose new clinical MIC breakpoints for antimicrobial susceptibility testing these bacteria isolated from dogs of ≤ 1, 2, and ≥ 4 μg/mL for the Susceptible, Intermediate, and Resistant category, respectively, for testing bacteria of the Enterobacterales, and values of ≤ 2, 4, and ≥ 8 μg/mL, respectively, for testing P. aeruginosa.

  PublisherDOI

• Effects of regional diversity on antimicrobial prescribing in dogs and cats in North Carolina from 2019 to 2020

  JAC-Antimicrobial Resistance · 2025-04-29 · 1 citations

  articleOpen access

  Background: Data on antimicrobial use (AMU) in companion animals is lacking in the United States, along with information regarding drivers of such prescribing. Objectives: To describe trends in AMU for dogs and cats in North Carolina (NC) over geography, urbanicity, time, and patient sex from 1 January 2019 to 31 December 2020 and evaluate the influence of summarized measures of social vulnerability and the COVID-19 pandemic on prescribing practices. Methods: In cooperation with IDEXX Laboratories, Inc. (IDEXX), we collected prescribing data from dogs and cats treated at 389 practices during 2019 and 2020. Practices were stratified by geographic region (mountain, piedmont, coastal plain) and urbanization (rural, urban). Social vulnerability was measured using the CDC published Social Vulnerability Index (SVI) data and was summarized for each of the six areas. Poisson family models were used to estimate prescribing rates and rate ratios for independent variables, normalized by the total number of monthly patients. Results: Combination beta-lactam agents, fluoroquinolones, nitroimidazole, and cephalosporins were the most prescribed drug classes. Region and urbanicity only significantly affected prescribing rate for first-generation cephalosporins in dogs, and prescribing rates did not significantly change during the COVID-19 pandemic. Patient sex was the most consistently significant independent variable for prescribing rates. Conclusions: The current study found that prescribing rates of the most common antimicrobials in dogs and cats were fairly uniform with some increased prescribing in rural and vulnerable areas of the state.

  PublisherOA PDFDOI

• Serum Symmetric Dimethylarginine as a Predictor of Toxicity of Carboplatin in Dogs

  Veterinary and Comparative Oncology · 2025-12-23

  articleOpen access

  ABSTRACT Glomerular filtration rate (GFR) predicts carboplatin clearance and myelotoxicity in humans and cats. This relationship is unknown in dogs. In canines, elevated serum symmetric dimethylarginine (SDMA) correlates with reduced GFR. This study prospectively evaluated whether dogs with elevated SDMA (> 14 μg/dL) are at increased risk of hematologic and gastrointestinal toxicity following carboplatin chemotherapy. Plasma samples were collected to determine if SDMA or other factors are significant determinants of carboplatin pharmacokinetics. Thirty client‐owned dogs weighing > 15 kg with confirmed neoplasia were enrolled. Dogs received carboplatin intravenously (300 mg/m 2 ). SDMA was measured on the day of treatment. Nonlinear mixed effects modelling was done to identify possible covariates affecting pharmacokinetic parameters. Adverse effects were monitored with weekly complete blood counts and owner assessment forms. Five dogs had elevated SDMA; four had significantly reduced carboplatin clearance (mean 93.9, range 76.1–116.8 mL/h/kg) compared with dogs with SDMA ≤ 14 μg/dL (mean 185.4, range 114.3–268.3 mL/h/kg, p < 0.001). Three dogs with elevated SDMA experienced grade 4 neutropenia; one was euthanized due to sepsis. Two additional dogs with elevated SDMA were euthanized 5‐ and 13‐days post treatment due to severe gastrointestinal signs. Twenty‐five dogs had SDMA ≤ 14 μg/dL: 10 had asymptomatic grade 3 or 4 neutropenia, 3 had grade 3 or 4 GI toxicity, and none died. Elevated SDMA was associated with decreased carboplatin clearance in dogs and predicted risk for treatment‐related toxicity and death in our study population.

  PublisherOA PDFDOI

• Pradofloxacin pharmacokinetics after oral and intravenous administration in dogs reveal plasma concentrations sufficient to treat infections caused by susceptible bacteria

  American Journal of Veterinary Research · 2025-09-03

  articleOpen access1st authorCorresponding

  Objective: To determine the pharmacokinetics of pradofloxacin following oral and IV administration of a concentrated solution available in the US and whether the plasma pradofloxacin concentration would be sufficient to treat susceptible bacterial infections. Methods: Pradofloxacin was administered orally and IV as a 200-mg/mL solution at a dose of 10 mg/kg to 6 healthy dogs in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected for the measurement of plasma pradofloxacin concentration via HPLC. Pharmacokinetic analysis was performed with nonlinear mixed-effects modeling. Results: After oral administration of pradofloxacin, the peak plasma concentration was 3.4 μg/mL, and the elimination half-life was 5.42 hours, with oral bioavailability of 69%. After IV administration, the elimination half-life was 8.1 hours, systemic clearance was 0.20 L/kg/h, and volume of distribution was 2.06 L/kg. Conclusions: There were no adverse effects from direct IV injection of pradofloxacin, and the drug was well absorbed when administered orally as the solution. Clinical Relevance: The concentrations from each route were sufficient to reach the free drug concentration area-under-the-curve/MIC ratio (fAUC/MIC) pharmacokinetic-pharmacodynamic targets for treating infections caused by gram-positive and gram-negative bacteria in the susceptible category of ≤ 0.25 μg/mL according to clinical breakpoints approved by the Clinical and Laboratory Standards Institute.

  PublisherDOI

• Antimicrobial use guidelines for canine pyoderma by the International Society for Companion Animal Infectious Diseases (ISCAID)

  Veterinary Dermatology · 2025-05-07 · 28 citations

  reviewOpen access

  BACKGROUND: Canine pyoderma is one of the most common presentations in small animal practice, frequently leading to antimicrobial prescribing. OBJECTIVES: To provide clinicians with antimicrobial treatment guidelines for staphylococcal pyoderma, including those involving meticillin-resistant staphylococci. Guidance on diagnosing surface, superficial and deep pyoderma and their underlying primary causes, is included. Recommendations aim to optimise treatment outcomes while promoting responsible antimicrobial use. MATERIALS AND METHODS: Evidence was gathered from a systematic literature review of English-language treatment studies for canine pyoderma up to 23 December 2023. Quality was assessed using SORT criteria and combined with authors' consensus evaluation. Recommendations were voted on in an iterative process, followed by a Delphi-style feedback process before final agreement by the authors. RESULTS: Cytology should be performed in all cases before antimicrobials are used. Topical antimicrobial therapy alone is the treatment-of-choice for surface and superficial pyodermas. Systemic antimicrobials should be reserved for deep pyoderma and for superficial pyoderma when topical therapy is not effective. Systemic therapy, with adjunctive topical treatment, is initially provided for 2 weeks in superficial and 3 weeks in deep pyoderma, followed by re-examination to assess progress and manage primary causes. First-choice drugs have expected efficacy against the majority of meticillin-susceptible Staphylococcus pseudintermedius; for all other drugs, laboratory testing should confirm susceptibility and exclude suitability of safer alternatives. As culture and susceptibility testing are essential for rationalising systemic therapy, laboratories and practices should price them reasonably to encourage use. Proactive topical therapy using antiseptics may help prevent recurrences. CONCLUSIONS AND CLINICAL RELEVANCE: The accessibility of the skin offers excellent, achievable opportunities for antimicrobial stewardship.

  PublisherOA PDFDOI

Frequent coauthors

• Butch KuKanich

  Kansas State University

  41 shared

• Craig A. Harms

  North Carolina State University

  37 shared

• Éric Honoré

  Institut de Pharmacologie Moléculaire et Cellulaire

  36 shared

• Fred DeGraves

  Western Kentucky University

  36 shared

• Steven C. Budsberg

  University of Georgia

  36 shared

• Derek M. Foster

  North Carolina State University

  27 shared

• João Brandão

  26 shared

• Thomas N. Tully

  Louisiana State University

  26 shared

Education

• Ph.D., Veterinary Science

  North Carolina State University

  2002

• M.S., Veterinary Science

  North Carolina State University

  1998

• B.S., Animal Science

  University of California, Davis

  1996

Awards & honors

• Zoetis Distinguished Veterinary Teacher Award
• Faculty Award presented to the outstanding teacher by veteri…
• Pfizer Award for Research Excellence
• Excellence in Consensus Management by the Clinical and Labor…
• Lloyd E.. Davis Award by the AAVPT