@article{ding_zeng_fung_chen_qiao_2001, title={Pharmacokinetics of sarafloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications}, volume={24}, ISSN={["1365-2885"]}, DOI={10.1046/j.1365-2885.2001.00348.x}, abstractNote={Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half‐lives (t1/2β) were 3.37 ± 0.46, 4.66 ± 1.34, 7.20 ± 1.92 (pigs) and 2.53 ± 0.82, 6.81 ± 2.04, 3.89 ± 1.19 h (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 ± 9.8 and 42.6 ± 8.2% (pigs) and 72.1 ± 8.1 and 59.6 ± 13.8% (broilers), respectively. Steady‐state distribution volumes (Vd(ss)) of 1.92 ± 0.27 and 3.40 ± 1.26 L/kg and total body clearances (ClB) of 0.51 ± 0.03 and 1.20 ± 0.20 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single‐dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 μg/mL.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Ding, HZ and Zeng, ZL and Fung, KF and Chen, ZL and Qiao, GL}, year={2001}, month={Oct}, pages={303–308} }
 @article{qiao_riviere_2000, title={Dermal absorption and tissue disposition of 3,3',4,4'-tetrachlorobiphenyl (TCB) in an ex vivo pig model: Assessing the impact of dermal exposure variables}, volume={6}, DOI={10.1179/oeh.2000.6.2.127}, abstractNote={Abstract TCB is one of the dioxin-like polychlorinated biphenyls (PCBs). This research was designed to help assess the risk of occupational and environmental TCB exposure. To evaluate exposure variables' effects on dermal absorption and cutaneous disposition 14C-TCB (40 μg/cm2) in acetone, methylene chloride, a water-acetone mixture, and a soil-based mixture were applied in an ex-vivo pig-skin-flap model (n = 4–5/treatment). Dermal absorption (0.11–0.66%,8 hr) and penetration (1.14–2.48 %) varied according to exposure conditions. Acetone and methylene chloride vehicles differed in absorption profiles and skin penetration patterns but were, similar in absorption amounts. Adding water to the acetone did not change absorption but did alter the penetration pattern. The non-occluded soil-based mixture showed more absorption than did the liquid vehicles (p < 0.05), but occlusion significantly (p < 0.05) decr'eased that absorption (0.66 → 0.29%, 8 hr) and penetration (2.48 → 1.11%). In conclusion, dermal absorption data from liquid-organic or aqueousorganic mixtures may underestimate the risk of exposure to TCB-contaminated soil.}, journal={International Journal of Occupational and Environmental Health}, author={Qiao, G. L. and Riviere, J. E.}, year={2000}, pages={127–137} }
 @article{baynes_monteiro-riviere_qiao_riviere_1997, title={Cutaneous toxicity of the benzidine dye direct red 28 applied as mechanistically-defined chemical mixtures (MDCM) in perfused porcine skin}, volume={93}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/s0378-4274(97)00083-0}, DOI={10.1016/S0378-4274(97)00083-0}, abstractNote={Complex chemical mixtures at hazardous waste sites can potentially consist of a marker chemical and several other chemicals, each of which can have different modulating actions on the dermatotoxicity of the marker chemical and/or other components in the mixture. A total of 16 mixtures, consisting of a marker chemical direct red 28 (DR28), a solvent (80% acetone or DMSO in water), a surfactant (0 or 10% sodium lauryl sulfate, SLS), a vasodilator (0 or 180 μg methyl nicotinate, MN) and a reducing agent (0 or 2% stannous chloride, SnCl2) were selected. Isolated perfused porcine skin flaps (IPPSFs), which have been proven to be an in vitro model for assessing absorption and toxicity, were utilized. These mixtures did not cause severe dermatotoxicity. However, light microscopic observations depicted minor alterations (intracellular and intercellular epidermal edema) with DMSO mixtures than with acetone mixtures. The presence of SLS caused an alteration in the stratum corneum. Enzyme histochemical staining for alkaline phosphatase (ALP) and nonspecific esterase (NSE) revealed no significant treatment effects, but increased staining for acid phosphatase (ACP) in the stratum basale was significant when associated with SLS or SLS+MN in DMSO mixtures. At 8 h post-dose, only DMSO mixtures containing SL+MN, SL+SnCl2, or SLS+MN+SnCl2 significantly increased transepidermal water loss. In conclusion, this study demonstrated that various mixtures, especially those containing SLS alter the epidermal barrier differently with complex interactions occurring simultaneously.}, number={2-3}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Baynes, Ronald E and Monteiro-Riviere, Nancy A and Qiao, Gui L and Riviere, Jim E}, year={1997}, month={Dec}, pages={159–169} }
 @article{qiao_brooks_riviere_1997, title={Pentachlorophenol dermal absorption and disposition from soil in swine: Effects of occlusion and skin microorganism inhibition}, volume={147}, ISSN={["1096-0333"]}, DOI={10.1006/taap.1997.8288}, abstractNote={Residue of the environmentally relevant biocide pentachlorophenol (PCP) is found mainly in soil, making dermal contact one of the primary routes for PCP exposure. To quantify exposure effects on dermal absorption and systemic disposition, [14C-UL]PCP was dosed nonocclusively or occlusively at 40 micrograms/cm2 in a soil-based mixture in an in vivo swine model. Additionally, antibiotics were also codosed with occlusive PCP in soil to examine the impacts of skin microbial PCP biodegradation on total dermal absorption. Under nonocclusive, occlusive, and occlusive-antibiotic conditions, total radiolabel absorption by 408 hr was 29.08, 100.72, and 86.21% dose, respectively. Tissue accumulation of PCP and its labeled metabolite(s) was very significant in swine since one-half to two-thirds of the absorbed dose was still present in tissues by 17 days after PCP dermal exposure. High 14C concentrations were found in liver, kidney, lung, ovary, and uterus. Urine and fecal routes were equally important for label excretion from the body. Occlusion enhanced total dermal absorption and changed the shape of the absorption profiles in the blood and plasma. Skin microorganism inhibition retarded 14C dermal absorption, altered local and systemic tissue distribution, and increased plasma/blood concentration ratios, suggesting skin microbial PCP degradation might play an important role in the altered absorption and disposition by occlusion. This study demonstrated significant dermal absorption and extensive tissue persistence of PCP after soil exposure. Occlusion and skin microflora growth may greatly impact dermal absorption, cutaneous disposition, and systemic toxic input. Therefore, exposure-specific PCP absorption and disposition profiles must be taken into consideration in risk analysis.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Qiao, GL and Brooks, JD and Riviere, JE}, year={1997}, month={Dec}, pages={234–246} }
 @book{riviere_brooks_qiao_monteiro-riviere_1997, title={Percutaneous absorption of volatile chemicals}, DOI={10.21236/ada332910}, abstractNote={Abstract : The purpose of this project was to assess the percutaneous absorption of two volatile organic compounds, chloropentafluorobenzene (CPFB) and dichlorobenzene (DCB) in the isolated perfused porcine skin flap (IPPSF) model. An independent theoretical goal was to begin to develop a mathematical framework to assess vehicle-compound interactions which occur during dermal exposure. Assessment of the percutaneous absorption and penetration of volatile compounds is difficult. The process of studying these compounds involved 5 steps: (1) development of an IPPSF cradle chamber to trap the evaporated compound in the area next to the skin, (2) assessment of the mass of CPFB that was absorbed into the perfusate from CPFB which was evaporated from excised skin, (3) exposure of the IPPSF to neat test compounds and test compounds in a vehicle, (4) assessment of the mass of the test compound in the perfusate is a result of exposure to the volatile compound vapor, and (5) development of a dosing dome that allowed dosing a vapor without vapor uptake directly into the perfusate. Relevant absorption parameters were then determined. These studies demonstrated dose-dependent absorption of CPFB and DCB in skin which was further modulated by concomitant exposure to vehicle. The data obtained could be used as direct input into a systemic risk assessment model.}, journal={(NTIS report AFOSR G49620-95-1-0017)}, institution={Bethesda, MD: Cambridge Scientific Abstracts}, author={Riviere, J. E. and Brooks, J. D. and Qiao, G. L. and Monteiro-Riviere, N.A.}, year={1997}, pages={1–23} }
 @article{qiao_brooks_baynes_monteiroriviere_williams_riviere_1996, title={The use of mechanistically defined chemical mixtures (MDCM) to assess component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals .1. Studies with parathion mixtures in isolated perfused porcine skin}, volume={141}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1996WC22200015&KeyUID=WOS:A1996WC22200015}, DOI={10.1006/taap.1996.0313}, abstractNote={Recently, attention has been directed to the risk assessment of cutaneous exposure to chemical mixtures rather than to only a single compound since this is the exposure scenario in the environment, residence, and work place. Using acetone or dimethylsulfoxide (DMSO) (80% in water) as a vehicle, percutaneous absorption and cutaneous disposition of parathion (PA) were studied following PA (40 microg/cm2) dosing on isolated perfused porcine skin as mechanistically defined chemical mixtures (MDCM) consisting of the surfactant sodium lauryl sulfate (SLS), the rubefacient methyl nicotinate (MNA), and the reducing agent stannous chloride (SnCl2). A full 2 x 4 factorial design was used to asses treatment effects and potential interactions. More radiolabel was absorbed with DMSO than with acetone albeit an earlier peak flux time but lower peak flux was observed with acetone than with DMSO. The absorption flux rate profiles with DMSO continued increasing but bipeak-featured profiles were observed with acetone. SLS enhanced PA absorption with both DMSO and acetone. The presence of MNA in both vehicles blunted the absorption rate curves without significantly changing total absorption. SnCl2 blocked PA absorption and increased residue level on the skin surface and in the stratum corneum (SC). The venous flux profiles were mixture-dependent and highly reproducible within treatment groups. Higher level interactions were also noted. This study indicated multiple levels of interactive effects on PA absorption which must be incorporated into any effort to identify critical mechanisms which affect risk assessment of topically exposed mixtures. It was suggested that the chemicals selected in a topically applied mixture may have significant effects on the penetration/distribution pattern and percutaneous absorption profile of a toxicant/drug in the mixture. The MDCM approach may be useful in a screening or triage approach to identify mixture components which affect marker chemical absorption as well as identify potential mechanisms which deserve further attention. Risk assessment efforts could then be focused on those mixtures, containing these critical components, which would be expected to have the greatest penetration and absorption.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Qiao, GL and Brooks, JD and Baynes, RE and MonteiroRiviere, NA and Williams, PL and Riviere, JE}, year={1996}, month={Dec}, pages={473–486} }
 @article{williams_thompson_qiao_monteiro-riviere_baynes_riviere_1996, title={The use of mechanistically defined chemical mixtures (MDCM) to assess mixture component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals .2. Development of a general dermatopharmacokinetic model for use in risk assessment}, volume={141}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1996WC22200016&KeyUID=WOS:A1996WC22200016}, DOI={10.1006/taap.1996.0314}, abstractNote={We present a conceptual approach to a general comprehensive mathematical model to quantify percutaneous absorption of topically applied chemicals in complex mixtures on the basis of biophysical parameters estimated or measured using in vitro and ex vivo perfused skin preparations. This model addresses mechanistically defined chemical mixtures (MDCM) which consist of components selected because of their potential to modulate by various mechanisms the absorption of a marker toxic penetrant. This model accounts for observed toxicodynamic general and specific effects of chemicals, acting single or in concert, on the absorption of any or all components in a defined mixture. We have also included experimental data from an isolated perfused porcine skin flap study with topically applied parathion as the marker penetrant and acetone or DMSO as solvent, with methyl nicotinate as a potential rubefacient, sodium laurel sulfate as a surfactant, and stannous chloride as a reducing agent in order to provide an illustration of the application and performance of the model. This model supports the MDCM concept that defining and then simulating those components of a complex mixture that could have a significant impact on the absorption of a marker toxic compound would be a useful screening approach in the risk assessment of topical chemical mixtures. It may also be used to identify critical pathways where chemical mixture component interactions significantly modify the absorption of the penetrant of interest.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Williams, P. L. and Thompson, D. and Qiao, G. L. and Monteiro-Riviere, N.A. and Baynes, R. L. and Riviere, J. E.}, year={1996}, month={Dec}, pages={487–496} }
 @article{qiao_riviere_1995, title={Significant Effects of Application Site and Occlusion on the Pharmacokinetics of Cutaneous Penetration and Biotransformation of Parathion in Vivo in Swine}, volume={84}, ISSN={0022-3549}, url={http://dx.doi.org/10.1002/jps.2600840408}, DOI={10.1002/jps.2600840408}, abstractNote={Increasing attention has been paid to the variables of application site and dosing method in quantitation of chemical percutaneous absorption. Following topical and intravenous application of [ring-U-14C]parathion (PA) in weanling pigs, we have determined, in a previous publication, the profiles of 14C and HPLC-separated paraoxon (PO), p-nitrophenol (PNP), and p-nitrophenyl beta-D-glucuronide (PNP-G) in plasma, urine, tissues, and dosing device. The purpose of the present paper was to analyze these data further, focusing on a quantitation of the effects of application site (back versus abdomen) and dosing method (occluded versus nonoccluded) on in vivo disposition of both the parent PA and its sequential metabolites PO, PNP, and PNP-G. Cutaneous and systemic disposition parameters were determined using a numerical simulation modeling approach and moments analysis. Mean systemic bioavailability values of 8.9-9.2% for abdomen and 14.7-19.7% for back were determined. Under different dosing conditions, 1-35% of the topical dose was metabolized dermally, and 9-19% systemically. Radioactivity in plasma and urine was predominantly contributed by PNP-G and PNP. Site differences in 14C percutaneous absorption were governed by the differences in transport of PA, PO, and PNP from epidermis into blood, by local tissue distribution, and by the cutaneous metabolism to PNP. Systemic bioavailability of PA was higher from the back than from the abdomen. Occlusion not only increased the amount of 14C absorption and shortened the mean residence time in most compartments but also altered the systemic versus cutaneous biotransformation pattern.(ABSTRACT TRUNCATED AT 250 WORDS)}, number={4}, journal={Journal of Pharmaceutical Sciences}, publisher={Elsevier BV}, author={Qiao, G.L. and Riviere, J.E.}, year={1995}, month={Apr}, pages={425–432} }
 @article{qiao_williams_riviere_1994, title={Percutaneous absorption, biotransformation and systemic disposition of parathion in vivo in swine. I. Comprehensive pharmacokinetic model}, volume={22}, journal={Drug Metabolism and Disposition}, author={Qiao, G. L. and Williams, P. L. and Riviere, J. E.}, year={1994}, pages={459–471} }
 @article{qiao_chang_riviere_1993, title={Effects of Anatomical Site and Occlusion on the Percutaneous Absorption and Residue Pattern of 2,6-(ring-14C)Parathion in Vivo in Pigs}, volume={122}, ISSN={0041-008X}, url={http://dx.doi.org/10.1006/taap.1993.1180}, DOI={10.1006/taap.1993.1180}, abstractNote={The effects of anatomical site and occlusion on the percutaneous absorption and residue pattern of total 14C were investigated following topical application of 2,6-[ring-14C]parathion onto four skin sites (300 micrograms/10 microCi; 40 micrograms/cm2) in weanling swine using occluded and nonoccluded dosing systems. The excretion profile was examined after iv administration. After dosing onto the abdomen, buttocks, back, and shoulder (N = 4/site), total urinary and fecal excretion (%dose) by 168 hr were, for the occluded system, 43.94 +/- 2.24, 48.47 +/- 7.85, 48.82 +/- 4.49, and 29.28 +/- 5.70%, and for the nonoccluded system, 7.47 +/- 2.16, 15.60 +/- 3.71, 25.00 +/- 8.75, and 17.41 +/- 1.76%, respectively. After iv dosing, 98.44 +/- 2.83% of the applied dose was excreted primarily via urine. The total recoveries for different sites ranged from 90.09 +/- 7.10 to 94.62 +/- 1.98% in the occluded system, 77.84 +/- 5.75 to 88.18 +/- 3.34% in the nonoccluded system, and 99.03 +/- 2.89% in the iv experiments. Time of maximal excretion rate was determined in the occluded system as abdomen (7.9 +/- 3.6 hr) < buttocks (9.4 +/- 2.6 hr) < shoulder (10.5 +/- 3.8 hr) < back (13.3 +/- 7.7 hr), but in the nonoccluded system as buttocks (11.9 +/- 3.6 hr) < shoulder (12.6 +/- 4.1 hr) < back (14.3 +/- 6.4 hr) < abdomen (16.9 +/- 7.1 hr). The percutaneous absorption from the shoulder was much lower than that from the other three sites under occluded conditions. However, if nonoccluded dosing was employed, absorption from the abdomen became the lowest, with shoulder and buttocks being similar, and the back the highest. Occlusion conceals the site difference and enhances both the extent and the rate of parathion percutaneous absorption in vivo. 14C residue pattern in tissues and dosing materials was site and dosing method dependent, all of which are factors which must be considered when assessing the risk of exposure to topically applied compounds.}, number={1}, journal={Toxicology and Applied Pharmacology}, publisher={Elsevier BV}, author={Qiao, G.L. and Chang, S.K. and Riviere, J.E.}, year={1993}, month={Sep}, pages={131–138} }