Enabling Technologies and
Oncograph™, a unique patient-derived sub-renal capsule Xenograft efficacy mouse model
BRIVAL™, in vitro drug metabolism
Bioanalytical LC/MS/MS Assays
ALIVE Laboratories™ Non-Human Primate Hepatocytes and Blood Products
- BRI is an exclusive distributor of Alive™ cynomology and rhesus monkey and other non-human primate hepatocytes, microsome, S9 and blood products (whole blood, plasma, serum) collected using a variety of anticoagulant.
- Please visit www.alivelaboratories.com for a list of products
Botanical Drug Development
- The use of integrated GC/MS and LC/MS assay strategies in the characterization of major and minor chemical components in botanical raw materials and natural health products
News Releases and Trade Publications
Biography of Dr. Albert P Li and Overview of BRIVAL™
BRIVAL™ is an affiliate of BRI Biopharmaceutical Research Inc. with expertise in the application of in vitro assays to aid define drug properties such as absorption, metabolism, drug-drug interactions, and toxicity (ADMET).
BRIVAL™ provides both GLP and nonGLP screening contract research service. The GLP studies are performed according to U. S. FDA and U. S. EPA GLP specifications, and should also satisfy most international regulatory agency requirements. The screening assays are aimed to provide rapid turn around to facilitate early drug discovery and development.
One of the major strengths of BRIVAL™ is the scientific excellence and extensive industrial experience of its senior staff. The two key senior staffs are Dr. Albert P. Li and Dr. David Kwok.
Dr. Albert P. Li is the President and CEO of BRIVAL™. Dr. Li has over 20 years of industrial experience in drug metabolism and toxicology. Dr. Li obtained his Ph. D. degree in 1976 from the Oak Ridge Graduate School of Biomedical Sciences, University of Tennessee. He was Director and Senior Fellow, Monsanto Company, St. Louis, Missouri; Research Professor and Director, Surgical Research Institute, St. Louis University Medical School, St. Louis, Missouri; Chief Scientific Officer, In Vitro Technologies Inc., Baltimore, Maryland; President and Chief Executive Officer, Phase 1 Molecular Toxicology, Santa Fe, New Mexico. Dr. Li is an internationally renowned scientist with over 150 publications and edited multiple books in his field. Dr. Albert Li has collaborated with U. S. FDA in the development and validation of in vitro drug-drug interaction assays.
Dr. David Kwok is an expert in Analytical Chemistry (especially in LC/MS analysis), with over 10 years of industrial experience. Dr. Kwok graduated from his pharmacy program in 1984 and Ph.D. in medicinal chemistry in 1991 from the University of British Columbia, Canada. He served in a variety of management and scientific posts at Health Canada from 1991 to 1998, involving herbal and botanical quality control, antimicrobial drug resistance and veterinary drug safety programs. He has been an invited speaker at numerous professional conferences and has contributed to over 30 scientific publications in bioanalytical chemistry applications and drug candidate optimization studies in peer-reviewed journals, poster presentations, and scientific review journals.
Ms. Clara Faan is a graduate of the Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada. Ms. Faan brings to BRIVAL™ over 15 years of industrial food/chemical laboratory managerial experience, including eight years at BRI as the Chief Operating Officer and VP Business Development. Ms Faans scientific experience and practical managerial effectiveness are the key success factors in the delivery of the many successful studies at BRIVAL™ and BRI.
Our laboratory has extensive experience in the application of in vitro experimental systems in the evaluation of drug properties. The following are examples of relevant publications by Dr. Albert P. Li and his colleagues:
- Kane, R. E., Li, A. P., and Kaminski, D. R. (1995). Sulfation and glucuronidation of acetaminophen by human hepatocytes cultured on matrigel and type 1 collagen reproduces conjugation in vivo. Drug Metabol. Disp. 23:303-307.
- Li, A. P., Xu, L., Rasmussen, A., Kaminski, D. L. (1995). Rifampicin induction of lidocaine metabolism in cultured human hepatocytes. J. Pharmacol. Exp. Therap. 274:673-677.
- Kier, L. D., Wagner, L. M., Wilson, T. V., Li, A. P., Short, R. D., and Kennedy, G. L. (1995). Cytotoxicity of ethylene oxide/propylene oxide copolymers in cultured mammalian cells. Drug Chem. Toxicol. 18: 29-41.
- Kaminski, D. L., Roque, M. A., Li, A. P. (1996). Role of protein kinase A in human hepatocyte DNA synthesis. Dig Dis Sci 41:1014-1021.
- Stratton, M. D., Sexe, R., Peterson, B., Kaminski, D. L., Li, A. P., Longo, W. E. (1996). The effect of trinitrobenzene sulfonic acid (TNB) on colonocyte arachinodonic acid metabolism. J Surg Res 60:375-378.
- Li, A. P. (1997). Evaluation of drug-drug interactions in primary human hepatocytes . In: Drug-drug Interactions: Scientific and Regulatory Perspectives, A. P. Li, Volume Editor. Advances in Pharmacology, 43: 103-130.
- Li, A. P. (1998). Applications of primary hepatocytes in drug metabolism and toxicology. Comments on Toxicology, 6: 199-220.
- Li, A. P., Maurel, J. P., Lechon-Gomez, M., Cheng, L. C. and Jurima-Romet, M. (1997). Preclinical evaluation of drug-drug interactions: present status of the application of primary human hepatocytes in the evaluation of cytochrome P450 induction. Chemico-Biological Interactions 107:5-16.
- Mattes, W. B. and Li, A. P. (1997). Quantitative reverse transcriptase/PCR assay for the measurement of induction in cultured hepatocytes. Chemico-Biological Interactions 107:47-61.
- Li, A. P. and Kedderis, G. L. (1997). Primary hepatocyte culture as an experimental model for the evaluation of interactions between xenobiotics and drug-metabolizing enzymes. Chemico-Biological Interactions 107:1-3.
- Ruegg, C. E., Silber, P. M., Mughal, R. A., Ismail, J., Lu, C. and Li, A. P. (1997) P450 induction in primary human hepatocytes after cryopreservation. In Vitro Toxicology 10:217-222.
- Jurima-Romet, M., Huang, H. S., Beck, D. J. and Li, A. P. (1996). Metabolism of terfenadine and its inhibition in primary human and rat hepatocytes and HepG2 cells. Toxicology in vitro 10: 655-663.
- Li, A. P., Reith, M. K., Rasmussen, A., Gorski, J. C., Hall, S. D., Xu, L., Kaminski, D. L., and Cheng, L. K. (1997). In vitro evaluation of drug-drug interaction potential: A comparison of rifampin, rifapentine, and rifabutin in cytochrome P450 3A induction potential in primary human hepatocytes. Chemico-Biological Interactions 107:17-30.
- Li, A. P. and Jurima-Romet, M. (1997). Applications of primary human hepatocytes in the evaluation of pharmacokinetic drug-drug interactions: Evaluation of model drugs terfenadine and rifampin. Cell Biology and Toxicology 13: 365-374.
- Li, A. P. (1998). Scientific Basis of Drug-Drug Interactions: Mechanism and preclinical evaluation. Drug Information Journal 32: 657-664.
- Li, A. P. and Jurima-Romet, M. Overview: Scientific Basis of Pharmacokinetic Drug-Drug Interactions. in Drug Interactions: Scientific and Regulatory Perspectives (Li, A. P., Volume Editor), Advances in Pharmacology, 43: 1 - 6.
- Li, A. P., D. J. Beck, L. J. Loretz, Lilly Xu, Asenath Rasmussen, Jill C. Merrill and Donald L. Kaminski (1997). Primary human hepatocytes as an in vitro toxicology system. In "Advances in Animal Alternatives for Safety and Efficacy Testing" (Editors: Harry Salem and Sidney A. Katz). Taylor and Francis, New York. Pp. 359-368.
- Masubuchi, N., Li, A. P., and Okazaki, O (1998). An evaluation of the cytochrome P450 induction potential of pantoprazole in primary human hepatocytes. Chemico-Biol. Interact. 114: 1-13.
- Li, A. P. (1998). Preclinical evaluation of drug-drug interactions using human in vitro experimental systems. IDrugs 1(3):311-314.
- Li, A. P. (1999). Overview: hepatocytes and cryopreservation a personal historical prespective. Chemico-Biological Interactions 121: 1-6.
- Li, A. P. , Lu, C., Brent, J. A., Pham, C., Fackett, A., Ruegg, C. E., Silber, P. M. (1999). Cryopreserved human hepatocytes: characterization of drug-metabolizing enzyme activities and applications in high throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential. Chemico-Biological Interactions 121:17-36.
- Li, A. P., Gorycki, P. D., Hengstler, J. G., Kedderis, G. L., Koebe, H. G., Rahmani, R., de Sousa, G., Silva, J. M., Skett, P. (1999). Present status of the application of cryopreserved hepatocytes in the evaluation of xenobiotics: consensus of an international expert panel. Chemico-Biological Interactions 121:117-122.
- Li, A. P., Hartman, N. R., Lu C., Collins, J. M., Strong, J. M. (1999). Effects of cytochrome P450 inducers on 17?-Ethynylestradiol (EE2) conjugation by primary human hepatocytes. British Journal of Clinical Pharmacology, 48:733-742.
- Xu L, Li AP, Kaminski DL, Ruh MF (2000). 2,3,7,8 Tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in cultured rat and human hepatocytes. Chem Biol Interact. 124(3):173-89.
- Li, AP (2000). Mechanism-based preclinical approaches for the evaluation of drug-drug interactions. Xenobiotic Metabolism and Disposition 15:228-234.
- MacGregor JT, Collins JM, Sugiyama Y, Tyson CA, Dean J, Smith L, Andersen M, Curren RD, Houston JB, Kadlubar FF, Kedderis GL, Krishnan K, Li AP, Parchment RE, Thummel K, Tomaszewski JE, Ulrich R, Vickers AE, Wrighton SA (2001). In vitro human tissue models in risk assessment: report of a consensus-building workshop. Toxicol Sci. 59(1):17-36.
- Lu, C and Li, AP (2001). Species comparison in P450 induction: effects of dexamethasone, omeprazole and rifampin on P450 isoforms 1A and 3A in primary hepatocytes from man, Sprague-Dawley rat, minipig and beagle dog. Chem. Biol. Interact. 134:271-281.
- Easterbrook, J., Fackett, D, Li, AP (2001). A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4-hydroxylation, chloroxazone 6-hydroxylation, and testosterone 6b-hydroxylation. Chem. Biol. Interact. 134:243-249.
- Li, A. P. (2002). ADME-Tox screening in drug discovery. In: Integrated Drug Discovery Technologies (Mei, H. Y. and Czarnik, A. W., Editors), Marcel Dekker Inc., New York and Basel. Pp. 289 318.
- Li, A. P. (2002). Foreword: Evaluation of Idiosyncratic Drug Toxicity. Chemico-Biol Interact 2002 Nov 10:142(1-2):1-3.
- Kapetanovic, I. M., Torchin, C. D., Strong, J. M., Yonekawa, W. D., Lu, C., Li, A. P., Dieckhaus, C. M., Santos, W. L., Macdonald, T. L., Sofia, R. D., and Kupferberg, H. J. (2002). Reactivity of atropaldehyde, a felbamate metabolite in human liver tissue in vitro. Chem Biol Interact. 2002 Nov 10;142(1-2):119-34.
- Lloyd, S. , Hayden, M. J., Sakai, Y., Fackett, A., Silber, P. M., Hewitt, N. J., and Li, A. P. (2002). Differential in vitro hepatotoxicity of troglitazone and rosiglitazone among cryopreserved human hepatocytes from thirty-seven donors. Chem Biol Interact. 2002 Nov 10;142(1-2):57-71.
- Prabhu, S., Fackett, A., Lloyd, S., McClellan, H. A., Terrell, C. M., Silber, P. M., Li, A. P. (2002), Identification of glutathione conjugates of troglitazone in human hepatocytes. Chem Biol Interact. 142(1-2):83-97. Hewitt, N. J., Lloyd, S., and Li, A. P. (2002). CYP3A4, glucuronyl transferasde and sulfotransferases as key determinants of troglitazone cytotoxicity in human hepatocytes. Chem Biol Interact. 2002 Nov 10;142(1-2):83-97.
- Shitara, Y., Itoh, T., Satoh, H., Li, A. P., and Sugiyama, Y. (2003). Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J. Pharmacol. Exp. Ther. 304:610-616.
- Li, A. P. A review of the common properties of drugs with idiosyncratic hepatotoxicity and the "multiple determinant hypothesis" for the manifestation of idiosyncratic drug toxicity. Chem Biol Interact. 2002 Nov 10;142(1-2):7-23.
- Shitara, Y., LI, A. P., Kato, Y., Lu, C., Ito, K., Itoh, T. and Sugiyama, Y. (2003). Function of uptake transporters for taurocholate and estradiol 17b-D-glucuronide in cryopreserved human hepatocytes. Drug Metabol. Pharmacokin. 18:33-41.
- Li, A. P. Advancing technologies for accelerated drug development.
Drug Discov Today. 2003 Mar 1;8(5):200-2.
- Lanika A. Brown, Linda M. Arterburn, Ana P. Miller, Nancy L. Cowger, Sonya M. Hartley, Annette Andrews, Paul M. Silber, Albert P. Li (2003). Maintenance of liver functions in rat hepatocytes cultured as spheroids in a rotating wall vessel. In Vitro Cellular & Developmental Biology Animal 39(1): 13-20.
- Li, A. P. In vitro approaches to evaluate ADMET drug properties.
Curr Top Med Chem. 2004;4(7):701-6.
- Li, A. P. In vitro experimental models for the blood-brain barrier.
Drug Discov Today. 2004 Mar 1;9(5):204-5.
- Hesse LM, Sakai Y, Vishnuvardhan D, Li AP, Von Moltke LL, Greenblatt DJ. Effect of bupropion on CYP2B6 and CYP3A4 catalytic activity, immunoreactive protein and mRNA levels in primary human hepatocytes: comparison with rifampicin. J Pharm Pharmacol. 2003 Sep;55(9):1229-39.
- Kier LD, Neft R, Tang L, Suizu R, Cook T, Onsurez K, Tiegler K, Sakai Y, Ortiz M, Nolan T, Sankar U, and Li AP. Applications of microarrays with toxicologically-relevant genes (tox genes) for the evaluation of chemical toxicants in Sprague Dawley rats in vivo and human hepatocytes in vitro. Mutation Research 2004: 549: 101-113.
- Li, AP. An integrated multidisciplinary approach to drug safety assessment. Drug Discovery Today 2004: 9(16): 687-693
- Oleson FB, Berman CL, Li AP. An evaluation of the P450 inhibition and induction potential of daptomycin in primary human hepatocytes. Chem Biol Interact. 2004 Nov 20;150(2):137-47.
- Li AP, Bode C, Sakai Y. A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells.
Chem Biol Interact. 2004 Nov 1;150(1):129-36.
- Li AP. A comprehensive approach for drug safety assessment. Chem Biol Interact. 2004 Nov 1;150(1):27-33.
- Li AP. Accurate prediction of human drug toxicity: a major challenge in drug development. Chem Biol Interact. 2004 Nov 1;150(1):3-7.
- Li AP. Preface. Chem Biol Interact. 2004 Nov 1;150(1):1.
- Zou L, Henderson GL, Harkey MR, Sakai Y, Li A. Effects of kava (Kava-kava, 'Awa, Yaqona, Piper methysticum) on c-DNA-expressed cytochrome P450 enzymes and human cryopreserved hepatocytes. Phytomedicine. 2004;11(4):285-94.
BOOKS/Special Journal Issues:
- A. P. Li and R. H. Heflich, Editors. Genetic Toxicology. CRC Press, Boca Raton (1991).
- A. P. Li (Editor-in-chief). Toxicity Testing: New Approaches and Applications in Human Risk Assessment. Raven Press, New York (1985).
- A. P. Li, Editor. Drug-Drug Interactions: Scientific and Regulatory Perspectives. (Vol. 43, Advances in Pharmacology Series). Academic Press, San Diego (1997).
- A. P. Li and G. L. Kedderis, Guest Editors. Special Issue: Cytochrome P450 Induction in Primary Cultured Hepatocytes. Chemico-Biological Interactions, Vol. 107, Nos. 1, 2 (1997).
- A. P. Li, Editor. Special Issue of Hepatocyte Reports: Hepatocyte Cryopreservation. Chemico-Biological Interactions, Vol. 121 (1999).
- A. P. Li, Editor. Special Issue: Idiosyncratic Drug Toxicity. Chemico-Biological Interactions 142 (2002).
- A. P. Li and Yuichi Sugiyama. Preclinical and Clinical Evaluation of Drug-Drug Interactions. ISE Press: Baltimore, MD. (2003).
- A. P. Li, Editor. Special Issue: Accurate Prediction of Human Drug Toxicity: Challenges, Strategies and Experimental Approaches. Chemico-Biological Interactions 150 (2004).