Differentiation of gut and hepatic first pass metabolism and secretion of saquinavir in ported rabbits

Journal of Pharmacology and Experimental Therapeutics

Volumn 310, Issue 1, 2004, Pages 359-366

  Sinko, Patrick J ^a   Kunta, Jeevan R ^a,b   Usansky, Helen H ^a   Perry, Barbara A ^c  

^a RUTGERS UNIVERSITY   (United States)

^b GLAXOSMITHKLINE   (United States)

^c ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOSPORIN A; CYTOCHROME P450 3A; ELACRIDAR; GLYCOPROTEIN P; MIDAZOLAM; SAQUINAVIR;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; ENZYME INHIBITION; FEMALE; FIRST PASS EFFECT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; INTESTINE ABSORPTION; LIVER METABOLISM; MASS SPECTROMETRY; MEAN RESIDENCE TIME; NONHUMAN; PORTAL VEIN; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RABBIT; SMALL INTESTINE;

ANIMALS; DIGESTIVE SYSTEM; FEMALE; HIV PROTEASE INHIBITORS; LIVER; P-GLYCOPROTEIN; RABBITS; SAQUINAVIR;

EID: 3042637099     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.103.064394     Document Type: Article

References (37)

1. Alsenz J, Steffen H, and Alex R (1998) Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharmacol Res 15:423-428.
2. Benet LZ, Cummins CL, and Wu CY (2003) Transporter-enzyme interactions: implications for predicting drug-drug interactions from in vitro data. Curr Drug Metab 4:393-398.
3. Boxenbaum H (1980) Interspecies variation in liver weight, hepatic blood flow and antipyrine intrinsic clearance: extrapolation of data to benzodiazepines and phenytoin. J Pharmacokinet Biopharmacol 8:165-176.
4. Brinkman K, Huysmans F, and Burger DM (1998) Pharmacokinetic interaction between saquinavir and cyclosporine. Ann Intern Med 129:914-915.
5. Edwards DJ, Fitzsimmons ME, Schuetz EG, Yasuda K, Ducharme MP, Warbasse LH, Woster PM, Schuetz JD, and Watkins PB (1999) 6′,7′- Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4 and P-glycoprotein. Clin Pharmacol Ther 65:237-244.
6. Fitzsimmons ME 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 25:256-266.
7. Georges E, Bradley G, Gariepy J, and Ling V (1990) Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc Natl Acad Sci USA 87:152-156.
8. Hicks CR and Turner KV Jr (1999) Fundamental Concepts in the Design of Experiments, 5th ed, pp 63-73, Oxford University Press, Inc., New York.
9. Hyafil F, Vergely C, Du Vignaud P, and Grand-Perret T (1993) In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res 53:4595-4602.
10. Kempf DJ, Marsh KC, Kumar G, Rodrigues AD, Denissen JF, McDonald E, Kukulka MJ, Hsu A, Granneman GR, Baroldi PA, et al. (1997) Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother 41:654-660.
11. Kim AE, Dintaman JM, Waddell DS, and Silverman JA (1998a) Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther 286:1439-1445.
12. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, and Wilkinson GR (1998b) The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Investig 101:289-294.
13. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, et al. (1999) Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharmacol Res 16:408-414.
14. Kolars JC, Lown KS, Schmiedlin-Ren P, Ghosh M, Fang C, Wrighton SA, Merion RM, and Watkins PB (1994) CYP3A gene expression in human gut epithelium. Pharmacogenetics 4:247-259.
15. Kunta JR, Perry BA, Sutyak JP, and Sinko PJ (2001) Development of a novel intestinal and vascular access port (IVAP) rabbit model to study regiospecific oral absorption pharmacokinetics. Comp Med 51:349-356.
16. Kwei GY, Alvaro RF, Chen Q, Jenkins HJ, Hop CE, Keohane CA, Ly VT, Strauss JR, Wang RW, Wang Z, et al. (1999) Disposition of ivermectin and cyclosporin A in CF-1 mice deficient in mdr1a P-glycoprotein. Drug Metab Dispos 27:581-587.
17. Letrent SP, Pollack GM, Brouwer KR, and Brouwer KL (1998) Effect of GF120918, a potent P-glycoprotein inhibitor, on morphine pharmacokinetics and pharmacodynamics in the rat. Pharmacol Res 15:599-605.
18. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ, et al. (1997) Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther 62:248-260.
19. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, and Schellens JH (2001) Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 7:935-941.
20. Malingre MM, Beijnen JH, Rosing H, Koopman FJ, Jewell RC, Paul EM, Ten Bokkel Huinink WW, and Schellens JH (2001) Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients. Br J Cancer 84:42-47.
21. Martin C, Berridge G, Higgins CF, Mistry P, Charlton P, and Callaghan R (2000) Communication between multiple drug binding sites on P-glycoprotein. Mol Pharmacol 58:624-632.
22. Martin C, Berridge G, Mistry P, Higgins C, Charlton P, and Callaghan R (1999) The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br J Pharmacol 128:403-411.
23. Merry C, Mulcahy F, Barry M, Gibbons S, and Back D (1997) Saquinavir interaction with midazolam: pharmacokinetic considerations when prescribing protease inhibitors for patients with HIV disease. AIDS 11:268-269.
24. Palkama VJ, Ahonen J, Neuvonen PJ, and Olkkola KT (1999) Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin Pharmacol Ther 66:33-39.
25. Polli JW, Jarrett JL, Studenberg SD, Humphreys JE, Dennis SW, Brouwer KR, and Woolley JL (1999) Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharmacol Res 16:1206-1212.
26. Rowland M and Tozer TN (1995) Clinical Pharmacokinetics, pp 152-160, Williams & Wilkins, Media, PA.
27. Schinkel AH, Wagenaar E, van Deemter L, Mol CA, and Borst P (1995) Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin and cyclosporin A. J Clin Investig 96:1698-1705.
28. Schuetz EG, Umbenhauer DR, Yasuda K, Brimer C, Nguyen L, Relling MV, Schuetz JD, and Schinkel AH (2000) Altered expression of hepatic cytochromes P-450 in mice deficient in one or more mdr1 genes. Mol Pharmacol 57:188-197.
29. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
30. Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, Borst P, Nooijen WJ, Beijnen JH, and van Tellingen O (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycopretein in the intestine. Proc Natl Acad Sci USA 94:2031-2035.
31. Thummel KE, O'Shea D, Paine MF, Shen DD, Kunze KL, Perkins JD, and Wilkinson GR (1996) Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol Ther 59:491-502.
32. Tsuji A, Terasaki T, Takabatake Y, Tenda Y, Tamai I, Yamashima T, Moritani S, Tsuruo T, and Yamashita J (1992) P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci 51:1427-1437.
33. Whalen RD, Tata PN, Burckart GJ, and Venkataramanan R (1999) Species differences in the hepatic and intestinal metabolism of cyclosporine. Xenobiotica 29:3-9.
34. Williams GC, Knipp GT, and Sinko PJ (2003) The effect of cell culture conditions on saquinavir transport and interactions using MDCKII Cells overexpressing hMDR1. J Pharm Sci 92:1957-1976.
35. Williams GC and Sinko PJ (1999) Oral absorption of the HIV protease inhibitors: a current update. Adv Drug Deliv Rev 39:211-238.
36. Wu CY, Benet LZ, Hebert MF, Gupta SK, Rowland M, Gomez DY, and Wacher VJ (1995) Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin Pharmacol Ther 58:492-497.
37. Yokogawa K, Takahashi M, Tamai I, Konishi H, Nomura M, Moritani S, Miyamoto K, and Tsuji A (1999) P-glycoprotein-dependent disposition kinetics of tacrolimus: studies in mdr1a knockout mice. Pharmacol Res 16:1213-1218.