Factors responsible for the variability of saquinavir absorption: Studies using an instrumented dog model

Pharmaceutical Research

Volumn 21, Issue 3, 2004, Pages 436-442

  Tam Zaman, Nuzhat ^a   Tam, Yun K ^a   Tawfik, Soheir ^a   Wiltshire, Hugh ^b  

^a Kinetana Group Inc   (Canada)

^b ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

First pass liver metabolism; HIV protease inhibitor; Instrumented dog study; Low bioavailability; Poor gut absorption; Saquinavir

Indexed keywords

SAQUINAVIR;

ARTICLE; CONTROLLED STUDY; DOG; DOSE LIVER FUNCTION RELATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG CLEARANCE; DRUG FORMULATION; DRUG METABOLISM; FEMALE; FIRST PASS EFFECT; FOOD INTAKE; INTESTINE ABSORPTION; LIVER BLOOD FLOW; LIVER CLEARANCE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; BIOAVAILABILITY; KINETICS; LIVER; METABOLISM; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; DOGS; INTESTINAL ABSORPTION; KINETICS; LIVER; SAQUINAVIR;

EID: 1542721103     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/B:PHAM.0000019296.47762.3f     Document Type: Article

References (22)

1. M. E. Fitzsimmons and J. M. Collins. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4. Drug Metab. Dispos. 25:256-266 (1997).
2. V. S. Kitchen, C. Skinner, K. Ariyoshi, E. A. Lane, I. B. Duncan, J. Burckhardt, H. U. Burger, K. Bragman, A. J. Pinching, and J. N. Weber. Safety and activity of saquinavir in HIV infection. Lancet 345:952-954 (1995).
3. S. Noble and D. Faulds. Saquinavir: A review of its pharmacology and clinical potential in the management of HIV infection. Drugs 52:93-112 (1996).
4. C. Merry, M. G. Barry, F. Mulcahy, M. Ryan, J. Heavey, J. F. Tjia, S. E. Gibbons, A. M. Breckenridge, and D. J. Back. Saquinavir pharmacokinetics alone and in combination with ritonavir in HIV-infected patients. AIDS 11:F29-F33 (1997).
5. M. Boffito, P. Carriero, L. Trentini, R. Raiteri, S. Bonora, A. Sinicco, H. E. Reynolds, P. G. Hoggard, D. J. Back, and G. Di Perri. Pharmacokinetics of saquinavir co-administered with cimetidine. J. Antimicrob. Chemother. 50:1081-1084 (2002).
6. W. Cameron, E. Sun, M. Markowitz, C. Farthing, D. McMahon, D. Poretz, C. Cohen, S. Follansbee, J. H. Mellors, A. Hsu, G. F. Granneman, R. Maki, M. Salgo, J. Court, and J. Leonard. Combination use of ritonavir and saquinavir in HIV-infected patients: preliminary safety and activity data. In: Program and Abstracts of the XI International Conference on AIDS: July 7-12, 1996; Vancouver, British Columbia, Canada. Abstract THB 934.
7. D. W. O'Brien, H. A. Semple, G. D. Molnar, Y. K. Tam, R. T. Coutts, R. V. Rajotte, and J. Bayens-Simmonds. A chronic conscious dog model for direct transhepatic studies in normal and pancreatic islet cell transplanted dogs. J. Pharmacol. Methods 25:157-170 (1991).
8. H. R. Wiltshire, K. J. Prior, J. Dhesi, F. Trach, M. Schlageter, and H. Schöenberger. The synthesis of labeled forms of saquinavir. J. Labelled Cpd. Radiopharm. 41:1103-1126 (1998).
9. N. G. Knebel, S. R. Sharp, and M. J. Madigan. Quantification of the anti-HIV drug saquinavir by high-speed on-line high performance liquid chromatography/tandem mass spectrometry. J. Mass Spectrometry 30:1149-1156 (1995).
10. C. Ediss and Y. K. Tam. An interactive computer program for determining areas bounded by drug concentration curves using Lagrange interpolation. J. Pharmacol. Toxicol. Methods 34:165-168 (1995).
11. H. A. Semple, Y. K. Tam, and R. T. Coutts. Hydralazine pharmacokinetics and interaction with food: an evaluation of the dog as an animal model. Pharm. Res. 7:274-279 (1990).
12. A. Skerjanec, S. Tawfik, and Y. K. Tam. Nonlinear pharmacokinetics of mibefradil in the dog. J. Pharm. Sci. 85:189-192 (1996).
13. J. Alsenz, H. Steffen, and R. Alex. Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharm. Res. 15:423-428 (1998).
14. C. B. Washington, H. R. Wiltshire, M. M. T. Moy, S. R. Harris, E. W. D. Hall, L. M. P. Weigl, Z. Liang, and T. F. Blaschke. The disposition of saquinavir in normal and P-glycoprotein deficient mice and in cultured cells. Drug Metab. Dispos. 28:1058-1062 (2000).
15. M. T. Huisman, J. W. Smit, H. R. Wiltshire, J. H. Beijnen, and A. H. Schinkel. Assessing safety and efficacy of directed P-glycoprotein inhibition to improve the pharmacokinetic properties of saquinavir coadministered with ritonavir. J. Pharmacol. Ther. 304:596-602 (2003).
16. V. D. Makhey, A. Guo, D. A. Norris, and P. Hu. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells. Pharm. Res. 15:1160-1167 (1998).
17. M. F. Paine, M. Khalighi, J. M. Fisher, D. D. Shen, K. L. Kunze, C. L. Marsh, J. D. Perkins, and K. E. Thummel. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J. Pharmacol. Exper. Ther. 283:1552-1562 (1997).
18. C. M. Perry and S. Noble. Saquinavir: soft-gel capsule formulation. A review of its use in patients with HIV infection. Drugs 55:461-486 (1998).
19. V. A. Eagling, H. Wiltshire, I. W. A. Whitcombe, and D. J. Back. CYP3A4 mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in-vitro. Xenobiotica 32:1-17 (2002).
20. H. H. T. Kupferschmidt, K. E. Fattinger, H. R. Ha, F. Follac, and S. Krähenbühl. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br. J. Clin. Pharmacol. 45:355-359 (1998).
21. K. S. Lown, D. G. Bailey, R. J. Fontana, S. K. Janardan, C. A. Adair, L. A. Fortiage, M. B. Brown, W. Guo, and P. B. Watkins. Grapefruit juice increases felodopine oral availability in humans by decreasing intestinal CYP3A protein expression. J. Clin. Invest. 99:2545-2553 (1997).
22. J. L. Steimer, B. Fotteler, R. Gieschke, H. Wiltshire, and N. Buss. Predicting the optimal dose of saquinavir via modelling of dose-exposure and exposure-effect relationships. In measurement and kinetics of in vivo drug effects. In M. Danhof and J. L. Steimer (eds.), Advances in Simultaneous Pharmacokinetic/Pharmacodynamic Modelling. Center for Drug Research, Leiden/ Amsterdam, 1998, pp. 79-86.