Reduction of saquinavir exposure by coadministration of loperamide: A two-way pharmacokinetic interaction

Clinical Pharmacokinetics

Volumn 43, Issue 14, 2004, Pages 1015-1024

  Mikus, Gerd ^a   Schmidt, Laila ^a   Burhenne, Jürgen ^a   Ding, Reinhard ^a   Riedel, Klaus Dieter ^a   Tayrouz, Yorki ^a   Weiss, Johanna ^a   Haefeli, Walter Emil ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DINORLOPERAMIDE; DRUG METABOLITE; LOPERAMIDE; NORLOPERAMIDE; PLACEBO; SAQUINAVIR; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG DISPOSITION; DRUG EFFICACY; DRUG EXPOSURE; DRUG METABOLISM; DRUG URINE LEVEL; FEMALE; HUMAN; HUMAN EXPERIMENT; LIQUID CHROMATOGRAPHY; MALE; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TANDEM MASS SPECTROMETRY;

ADULT; AREA UNDER CURVE; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; FEMALE; HUMANS; LOPERAMIDE; MALE; MIDDLE AGED; SAQUINAVIR;

EID: 4744367091     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-200443140-00004     Document Type: Article

References (46)

1. Fitzsimmons ME, Collins JM. 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 1997; 25 (2): 256-66
2. Alsenz J, Steffen H, Alex R. Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharm Res 1998; 15 (3): 423-8
3. Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998; 101 (2): 289-94
4. Lee CG, Gottesman MM, Cardarelli CO, et al. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 1998; 37 (11): 3594-601
5. Profit L, Eagling VA, Back DJ. Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors. AIDS 1999; 13 (13): 1623-7
6. Washington CB, Wiltshire HR, Man M, et al. The disposition of saquinavir in normal and P-glycoprotein deficient mice, rats, and in cultured cells. Drug Metab Dispos 2000; 28 (9): 1058-62
7. Huisman MT, Smit JW, Wiltshire HR, et al. P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol 2001; 59 (4): 806-13
8. Merry C, Barry MG, Mulcahy F, et al. Saquinavir pharmacokinetics alone and in combination with ritonavir in HIV-infected patients. AIDS 1997; 11 (4): F29-33
9. Martin-Facklam M, Burhenne J, Ding R, et al. Dose-dependent increase of saquinavir bioavailability by the pharmaceutic aid Cremophor EL. Br J Clin Pharmacol 2002; 53 (6): 576-81
10. Flexner C. HIV-protease inhibitors. N Engl J Med 1998; 338 (18): 1281-92
11. Sherman DS, Fish DN. Management of protease inhibitor-associated diarrhoea. Clin Infect Dis 2000; 30 (6): 908-14
12. Schinkel AH, Wagenaar E, Mol CA, et al. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996; 97 (11): 2517-24
13. Sadeque AJ, Wandel C, He H, et al. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther 2000; 68 (3): 231-7
14. Tayrouz Y, Ganssmann B, Ding R, et al. Ritonavir increases loperamide plasma concentrations without evidence for P-glycoprotein involvement. Clin Pharmacol Ther 2001; 70 (5): 405-14
15. Wandel C, Kim RB, Kajiji S, et al. P-glycoprotein and cytochrome P450 3A inhibition: dissocation of inhibitory potencies. Cancer Res 1999; 59 (16): 3944-8
16. World Medical Association. Declaration of Helsinki [online]. Available from URL: http://www.health.gov.au/nhmrc/issues/helsinki.htm [Accessed 2004 Sep 7]
17. Stüven T, Griese EU, Kroemer HK, et al. Rapid detection of CYP2D6 null alleles by long distance- and multiplex-polymerase chain reaction. Pharmacogenetics 1996; 6 (5): 417-21
18. Nauck M, Stein U, von Karger S, et al. Rapid detection of the C3435T polymorphism of multidrug resistance gene 1 using fluorogenic hybridization probes. Clin Chem 2000; 46 (12): 1995-7
19. Cascorbi I, Gerloff T, Johne A, et al. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 2001; 69 (3): 169-74
20. Experimental Design Generator And Randomiser (EDGAR) [online]. Available from URL: http://www.jic.bbsrc.ac.uk/services/statistics/edgar.htm [Accessed 2004 Aug 17]
21. Ganßmann B, Klingmann A, Burhenne J, et al. Simultaneous determination of loperamide and its desmethylated metabolites in plasma and urine by high-performance liquid chromatography-atmosheric-pressure ionization mass spectrometry. Chromatographia 2001; 53 (11/12): 656-60
22. Burhenne J, Riedel KD, Martin-Facklam M, et al. Highly sensitive determination of saquinavir in biological samples using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 784 (2): 233-42
23. von Moltke LL, Greenblatt DJ, Grassi JM, et al. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol 1998; 38 (2): 106-11
24. von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of desipramine hydroxylation (cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci 1998; 87 (10): 1184-9
25. Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol 1997; 44 (2): 190-4
26. Grub S, Bryson H, Goggin T, et al. The interaction of saquinavir (soft gelatin capsule) with ketoconazole, erythromycin and rifampicin: comparison of the effect in healthy volunteers and in HIV-infected patients. Eur J Clin Pharmacol 2001; 57 (2): 115-21
27. Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med 2001; 2 (2): 105-13
28. Kempf DJ, Marsh KC, Kumar G, et al. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother 1997; 41 (3): 654-60
29. van Heeswijk RP, Veldkamp A, Mulder JW, et al. Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience. Antivir Ther 2001; 6 (4): 201-29
30. Piscitelli SC, Burstein AH, Weiden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002; 34 (2): 234-8
31. Moyle GJ, Buss NE, Goggin T, et al. Interaction between saquinavir soft-gel and rifabutin in patients infected with HIV. Br J Clin Pharmacol 2002; 54 (2): 178-82
32. John L, Marra F, Ensom MH. Role of therapeutic drug monitoring for protease inhibitors. Ann Pharmacother 2001; 35 (6): 745-54
33. Branch RA, Adedoyin A, Frye RF, et al. In vivo modulation of CYP enzymes by quinidine and rifampin. Clin Pharmacol Ther 2000; 68 (4): 401-11
34. De Luca A, Coupar IM. Insights into opioid action in the intestinal tract. Pharmacol Ther 1996; 69 (2): 103-15
35. Vincent J, Hunt T, Teng R, et al. The pharmacokinetic effects of coadministration of morphine and trovafloxacin in healthy subjects. Am J Surg 1998; 176 (6A Suppl.): 32-8S
36. Adelhoj B, Petring OU, Ibsen M, et al. Buprenorphine delays drug absorption and gastric emptying in man. Acta Anaesthesiol Scand 1985; 29 (6): 599-601
37. Kupferschmidt HHT, Fattinger KE, Ha HR, et al. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br J Clin Pharmacol 1998; 45 (4): 355-9
38. Eagling VA, Wiltshire H, Whitcombe IW, et al. CYP3A4-mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in vitro. Xenobiotica 2002; 32 (1): 1-17
39. Kim AE, Dintaman JM, Waddell DS, et al. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther 1998; 286 (3): 1439-45
40. Wandel C, Kim R, Wood M, et al. Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology 2002; 96 (4): 913-20
41. Weiss J, Burhenne J, Riedel KD, et al. Poor solubility limiting significance of in-vitro studies with HIV protease inhibitors. AIDS 2002; 16 (4): 674-6
42. Palkama VJ, Ahonen J, Neuvonen PJ, et al. Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin Pharmacol Ther 1999; 66 (1): 33-9
43. Buss N. Saquinavir soft gel capsule (Fortovase®): pharmacokinetics and drug interactions [abstract]. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1-5; Chicago
44. Muirhead GJ, Wulff MB, Fielding A, et al. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol 2000; 50 (2): 99-107
45. Cameron DW, Japour AJ, Xu Y, et al. Ritonavir and saquinavir combination therapy for the treatment of HIV infection. AIDS 1999; 13 (2): 213-24
46. Wacher VJ, Wu CV, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrorae P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog 1995; 13 (3): 129-34