@article{messenger_wofford_papich_2016, title={Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration}, volume={39}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12233}, abstractNote={Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK / PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid ( ISF ) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy B eagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC . Prostaglandin E 2 ( PGE 2 ) concentrations were quantified in ISF using ELISA . Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF . Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half‐life ( T ½) was longer in the ISF compared with plasma. PGE 2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF , and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un‐inflamed tissues.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Messenger, K. M. and Wofford, J. A. and Papich, M. G.}, year={2016}, month={Feb}, pages={32–39} } @article{bizikova_linder_wofford_mamo_dunston_olivry_2015, title={Canine epidermolysis bullosa acquisita: A retrospective study of 20 cases}, volume={26}, number={6}, journal={Veterinary Dermatology}, author={Bizikova, P. and Linder, K. E. and Wofford, J. A. and Mamo, L. B. and Dunston, S. M. and Olivry, T.}, year={2015}, pages={441-} } @article{olivry_wofford_paps_dunston_2011, title={Stratum corneum removal facilitates experimental sensitization to mite allergens in atopic dogs}, volume={22}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952348135&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2010.00938.x}, abstractNote={Abstract In humans with atopic dermatitis and in mouse models of IgE‐mediated allergic diseases, evidence is mounting that the stratum corneum (SC) provides an important barrier against environmental allergens. At this time, it is not known whether the SC has a similar role in dogs, especially in those with atopic dermatitis. The objectives of this pilot study were to determine whether SC removal led to earlier and stronger sensitization of atopic dogs to Dermatophagoides farinae (Df) house dust mites. Five Maltese‐beagle atopic (MBA) dogs were sensitized epicutaneously after the SC was removed with ten tape strips (TS group), while sensitization was done without tape strips in five other MBA dogs (nontape stripping; NTS group). During this 16 week study, sensitization was assessed with allergen‐specific IgE serology, intradermal testing with Df allergens and determination of stimulation indices of blood mononuclear cells cultured with Df and stained for CD4 and the activation markers CD25 or CD30. Compared with dogs from the NTS group, those of the TS group exhibited earlier rises in Df‐specific IgE serum levels, usually had higher allergen‐specific IgE titres, showed higher intradermal test reactivity and had earlier increases and higher percentages of CD25‐ or CD30‐positive activated allergen‐specific peripheral CD4‐positive T lymphocytes. These observations implicate a role of the SC as a barrier limiting sensitization to exogenous allergens in this experimental atopic dog model.}, number={2}, journal={VETERINARY DERMATOLOGY}, author={Olivry, Thierry and Wofford, Jessica and Paps, Judy S. and Dunston, Stanley M.}, year={2011}, month={Apr}, pages={188–196} }