Mechanistic simulations explain paradoxical saquinavir metabolism during in vitro vectorial transport study

Proceedings of the 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS'08 - "Personalized Healthcare through Technology"

Volumn , Issue , 2008, Pages 5462-5465

  Lam, Tai Ning ^a   Hunt, C Anthony ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

METABOLITES;

CACO-2 CELLS; IN-SILICO; IN-VITRO; SAQUINAVIR; SYNTHETIC METHODS;

DRUG DOSAGE;

HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; SAQUINAVIR;

ACTIVE TRANSPORT; ARTICLE; BIOLOGICAL MODEL; CACO 2 CELL LINE; COMPUTER SIMULATION; HUMAN; METABOLIC CLEARANCE RATE; PHYSIOLOGY; SIGNAL TRANSDUCTION;

BIOLOGICAL TRANSPORT, ACTIVE; CACO-2 CELLS; COMPUTER SIMULATION; HIV PROTEASE INHIBITORS; HUMANS; METABOLIC CLEARANCE RATE; MODELS, BIOLOGICAL; SAQUINAVIR; SIGNAL TRANSDUCTION;

EID: 61849112761     PISSN: None     EISSN: None     Source Type: Conference Proceeding    
DOI: 10.1109/iembs.2008.4650450     Document Type: Conference Paper

References (14)

1. Mouly SJ, Paine MF, Watkins PB. (2004) "Contributions of CYP3A4, P-glycoprotein, and Serum Protein Binding to the Intestinal First-Pass Extraction of Saquinavir" J Pharmacol Exp Ther. 308: 941-48.
2. Liu Y and Hunt CA (2006) "Mechanistic study of the cellular interplay of transport and metabolism using the synthetic modeling method." Pharm Res 23: 493-505.
3. Garmire LX and Hunt CA (2008) "In Silico Methods for Unraveling the Mechanistic Complexities of Intestinal Absorption: Metabolism-Efflux Transport Interactions." Drug Metab Dispos. 36: 1414-24.
4. Hunt CA, Ropella GE, Yan L, Hung DY and Roberts MS (2006). "Physiologically based synthetic models of hepatic disposition." J Pharmacokinet Pharmacodyn. 33: 737-72.
5. Garmire LX, Garmire DG, and Hunt CA (2007) "An in silico transwell device for the study of drug transport and drug-drug interactions." Pharm Res 24: 2171-86.
6. Yan L, Ropella GE, Park S, Roberts MS, Hunt CA (2007) "Modeling and Simulation of Hepatic Drug Disposition Using a Physiologically Based, Multi-agent In Silico Liver." Pharm Res 25: 1023-36.
7. Yan L, Sheihk-Bahaei S, Park S, Ropella GE, Hunt CA (2008) "Predictions of Hepatic Disposition Properties Using a Mechanistically Realistic, Physiologically Based Model." Drug Metab Dispos. 36: 759-68.
8. Yan L, Park S, Sheihk-Bahaei S, Ropella GEP, and Hunt CA (2008) Predicting hepatic disposition properties of cationic drugs using a physiologically based, agent-oriented In Silico Liver. Proceedings of the 2008 Agent-Directed Simulation Symposium (Yilmaz L, et al. eds); 2008 April 14-16; Ottawa, ON, pp. 162-69, SCS Press, San Diego, CA(ISBN: 1-56555-319-5).
9. Fitzsimmons MF. and Collins JM (1997). "Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4: potential contribution to high first-pass metabolism." Drug Metab Dispos 25:256 66.
10. Eagiing VA, Wiltshire H, Whitcombe IW, Back DJ. (2002) "CYP3A4-mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in vitro." Xenobiotica. 2002 Jan;32(1): 1-17.
11. Hochman JH, Chiba M, Nishime J, Yamazaki M, and Lin JH (2000) "Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4." J Pharmacol Exp Ther 292:310-18.
12. Gan LS, Moseley MA, Khosla B, Augustijns PF, Bradshaw TP, Hendren RW, and Thakker DR (1996) "CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells." Drug Metab Dispos 24:344-49.
13. Fisher J and Henzinger TA (2007) Executable cell biology. Nat Biotech 25: 1239-49.
14. Hunt CA, Ropella GEP, Park S, and Engelberg J (2008) "Dichotomies Between Computational and Mathematical Models." Nat Biotech 26: 737-8.