@article{merwe_brooks_gehring_baynes_monteiro-riviere_riviere_2006, title={A physiologically based pharmacokinetic model of organophosphate dermal absorption}, volume={89}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000233991000018&KeyUID=WOS:000233991000018}, DOI={10.1093/toxsci/kfj014}, abstractNote={The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to toxic chemicals and for the development of topically applied drugs, barriers, insect repellents, and cosmetics. In vitro flow-through cells offer a convenient method for the study of dermal absorption that is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model developed to simulate the absorption of organophosphate pesticides, such as parathion, fenthion, and methyl parathion through porcine skin with flow-through cells. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Three parameters were optimized based on experimental dermal absorption data, including solvent evaporation rate, diffusivity, and a mass transfer factor. Diffusion cell studies were conducted to validate the model under a variety of conditions, including different dose ranges (6.3-106.9 microg/cm2 for parathion; 0.8-23.6 microg/cm2 for fenthion; 1.6-39.3 microg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5-120 microl for ethanol; 20-80 microl for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools that may be used for in silico hypotheses generation and limited hypotheses testing. The similarity between the overall shapes of the experimental and model-predicted flux/time curves and the successful simulation of altered system conditions for this series of small, lipophilic compounds indicated that the absorption processes that were described in the model successfully simulated important aspects of dermal absorption in flow-through cells. These data have direct relevance to topical organophosphate pesticide risk assessments.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Merwe, D and Brooks, JD and Gehring, R and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2006}, month={Jan}, pages={188–204} }
 @article{gehring_baynes_riviere_2006, title={Application of risk assessment and management principles to the extralabel use of drugs in food-producing animals}, volume={29}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2006.00707.x}, abstractNote={A risk assessment of the food safety implications of drugs used in food‐producing animals is an essential component of the regulatory approval process for products containing these drugs. This ensures that there is negligible risk to human health if these drugs are used according to the instructions that appear on the approved label. A relative paucity of approved products for veterinary species; however, forces veterinarians worldwide to use drugs in an extralabel manner to treat disease and alleviate suffering in animals. In food‐producing animals, this may result in residues that are potentially harmful to the human consumer. This review describes how risk assessment principles can be extended to evaluate the risks posed by different classes of extralabel drug use. Risk management practices in the United States and Europe are summarized and contrasted to illustrate the application of these principles.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Gehring, R and Baynes, RE and Riviere, JE}, year={2006}, month={Feb}, pages={5–14} }
 @article{gehring_haskell_payne_craigmill_webb_riviere_2005, title={Aminoglycoside residues in food of animal origin}, volume={227}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2005.227.63}, abstractNote={Vet Med Today: FARAD Digest 63 T aminoglycoside antimicrobials are polar organic bases with bactericidal activity mostly against aerobic gram-negative bacteria. The group includes dihydrostreptomycin, streptomycin, neomycin, kanamycin, gentamicin, and amikacin. Use of this group of antimicrobials has declined because of resistance, particularly in the older drugs, and problems with toxicity, but they still remain important in the treatment of serious gramnegative infections in animals. They are also a common source of violative antimicrobial residues in food of animal origin. A number of veterinary organizations, including the Academy of Veterinary Consultants, the Society for Theriogenology, the American Association of Bovine Practitioners, the AVMA, and several state veterinary medical associations, have established or support policies that discourage the extralabel use of aminoglycosides. The purpose of this digest is to give an overview of the pharmacokinetics and other properties of the aminoglycosides that contribute to these residues so that practitioners can better understand the food-safety risks of using these antimicrobials in foodproducing animals.}, number={1}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Gehring, R and Haskell, SR and Payne, MA and Craigmill, AL and Webb, AI and Riviere, JE}, year={2005}, month={Jul}, pages={63–66} }
 @article{kukanich_gehring_webb_craigmill_riviere_2005, title={Effect of formulation and route of administration on tissue residues and withdrawal times}, volume={227}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2005.227.1574}, abstractNote={The formulation of a drug can have profound effects on tissue residues and, consequently, withdrawal times (WDTs) in food animal species. The WDT is the time after completion of treatment needed for tissue concentrations of the drug and any metabolites to decrease to less than the tolerance value or drug concentrations considered safe for human consumption. A drug can have a zero WDT if, after administration, the concentrations in the tissues are less than the tolerance value. A more thorough review of WDTs and tolerances and how they are determined has been published. 1}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={KuKanich, B and Gehring, R and Webb, AI and Craigmill, AL and Riviere, JE}, year={2005}, month={Nov}, pages={1574–1577} }
 @article{smith_gehring_craigmill_webb_riviere_2005, title={Extralabel intramammary use of drugs in dairy cattle}, volume={226}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2005.226.1994}, abstractNote={xtralabel intramammary administration of drugsoccurs with some regularity in dairy cattle, mostcommonly in association with mammary gland infec-tions (mastitis) that fail to respond to approved prod-ucts. To comply with AMDUCA regulations, extralabeldrug use must include a sufficiently extended with-drawal interval so that no residues are found in meat ormilk products. This is particularly important whenusing products via intramammary administrationbecause milk residue violations can have serious eco-nomic consequences for the producer and veterinarian.For some of the drugs listed in this report, well-con-ducted pharmacokinetic studies have been performedto define appropriate withdrawal intervals after intra-mammary administration in cattle, whereas for others,the recommendations may have been formulated onthe basis of limited data. To ensure food safety andavoid residue violations, it is extremely important forveterinarians to maintain good records and followextended withdrawal intervals when using intramam-mary administration of drugs in an extralabel manner.Producers should also be requested to test milk sam-ples from treated cows with an appropriate rapidresidue screening assay when a drug residue might bepresent. CeftiofurCeftiofur sodium}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Smith, GW and Gehring, R and Craigmill, AL and Webb, AI and Riviere, JE}, year={2005}, month={Jun}, pages={1994–1996} }
 @article{gehring_merwe_pierce_baynes_craigmill_riviere_2005, title={Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle}, volume={66}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2005.66.108}, abstractNote={Abstract}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gehring, R and Merwe, D and Pierce, AN and Baynes, RE and Craigmill, AL and Riviere, JE}, year={2005}, month={Jan}, pages={108–112} }
 @article{gehring_baynes_wang_craigmill_riviere_2004, title={A web-based decision support system to estimate extended withdrawal intervals}, volume={44}, ISSN={["1872-7107"]}, DOI={10.1016/j.compag.2004.05.002}, abstractNote={All drugs approved for use in food-producing animals have a withdrawal interval to prevent residues in food of animal origin that are potentially harmful to consumers. These withdrawal times must be appropriately extended if the drug is used in an extralabel manner. This paper describes a web-based application that was developed to facilitate the calculation of extended withdrawal intervals based on information in the databases maintained by members of the Food Animal Residue Avoidance Databank (FARAD) and using the Extrapolated Withdrawal Interval Estimator (EWE) algorithm. The implementation of this application was illustrated using a group of antimicrobials that are used in cattle and swine. The use of this application has been limited to staff veterinarians working for FARAD since limitations in the available pharmacokinetic data require that results are interpreted by personnel with in-depth knowledge of the pharmacokinetics of drugs in food-producing animals.}, number={2}, journal={COMPUTERS AND ELECTRONICS IN AGRICULTURE}, author={Gehring, R and Baynes, RE and Wang, J and Craigmill, AL and Riviere, JE}, year={2004}, month={Aug}, pages={145–151} }
 @article{smith_gehring_riviere_yeatts_baynes_2004, title={Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows}, volume={224}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2004.224.1827}, DOI={10.2460/javma.2004.224.1827}, abstractNote={Abstract}, number={11}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Smith, Geof W. and Gehring, Ronette and Riviere, Jim E. and Yeatts, James L. and Baynes, Ronald E.}, year={2004}, month={Jun}, pages={1827–1830} }
 @article{gehring_baynes_craigmill_riviere_2004, title={Feasibility of using half-life multipliers to estimate extended withdrawal intervals following the extralabel use of drugs in food-producing animals}, volume={67}, ISSN={["0362-028X"]}, DOI={10.4315/0362-028X-67.3.555}, abstractNote={Under the Animal Medicinal Drug Use Clarification Act of 1994, veterinarians are legally allowed to use drugs in food-producing animals in an extralabel manner. This could potentially lead to violative residues in food of animal origin. It is therefore essential that an appropriately extended withdrawal interval be established. Ideally, these extended withdrawal intervals should be calculated on the basis of the tissue half-life of the drug in the target animal. However, these data are not readily available for all drugs of extralabel use in food-producing animals. For this reason, the use of a half-life multiplier has been proposed as a simple alternative method to estimate the effective tissue half-life of a drug. Extended withdrawal intervals, estimated using various half-life multipliers, were compared with the withdrawal intervals calculated using actual tissue half-lives. For the group of drugs investigated, a half-life multiplier of 5 resulted in estimates of extended withdrawal intervals that were potentially inadequate to prevent violative tissue residues for drugs that had relatively long tissue half-lives, high tolerances, or both. This is possibly because fewer half-lives are required for these drugs to reach the target tissue concentrations following administration at label doses. Use of a smaller half-life multiplier (in this case 3) is therefore suggested to ensure that extended withdrawal intervals are adequate to prevent violative tissue residues.}, number={3}, journal={JOURNAL OF FOOD PROTECTION}, author={Gehring, R and Baynes, RE and Craigmill, AL and Riviere, JE}, year={2004}, month={Mar}, pages={555–560} }
 @article{craigmill_miller_gehring_pierce_riviere_2004, title={Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin G}, volume={27}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2004.00606.x}, abstractNote={Investigators frequently face the quandary of how to interpret the oftentimes disparate pharmacokinetic parameter values reported in the literature. Combining of data from multiple studies (meta‐analysis) is a useful tool in pharmacokinetics. Few studies have explored the use of meta‐analysis for veterinary species. Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta‐analysis. Therefore, in this study we performed a meta‐analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle. The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points). Three methods were used to calculate the parameters. The first was a simple statistical analysis of the parameter values reported in each paper. The second method was a standard Two‐Stage Method (TSM) using the mean concentration vs. time data extracted from each paper. The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs. time data reported in the various papers, treating the mean data as if each set came from an individual animal. The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG. The only significant difference noted was for OTC absorption half‐lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation. The NMEM procedure offers the possibility of including covariates such as dose, age, and weight. In this study the covariates did not influence the derived parameters. A combination approach to meta‐analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Craigmill, AL and Miller, GR and Gehring, R and Pierce, AN and Riviere, JE}, year={2004}, month={Oct}, pages={343–353} }
 @article{wang_gehring_baynes_webb_whitford_payne_fitzgerald_craigmill_riviere_2003, title={Evaluation of the advisory services provided by the Food Animal Residue Avoidance Databank}, volume={223}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2003.223.1596}, abstractNote={JAVMA, Vol 223, No. 11, December 1, 2003 A part of its mission to help ensure that foods of animal origin are free of violative chemical residues, the Food Animal Residue Avoidance Databank (FARAD) offers 2 advisory services to veterinary practitioners. The first is a comprehensive online database (VetGRAM) of drugs approved by the US FDA/Center for Veterinary Medicine (CVM) for the treatment of food-producing animals. Second, FARAD offers expert-mediated advice on residue avoidance and mitigation for chemical contamination incidents and the extralabel use of drugs. This service is provided by FARAD pharmacologists and toxicologists, who can be reached by e-mail as well as a toll-free telephone number.}, number={11}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Wang, JM and Gehring, R and Baynes, RE and Webb, AI and Whitford, C and Payne, MA and Fitzgerald, K and Craigmill, AL and Riviere, JE}, year={2003}, month={Dec}, pages={1596–1598} }