Modeling and simulation approach to support dosing and study design requirements for treating HIV-related neuropsychiatric disease with the NK1-R antagonist aprepitant

Current HIV Research

Volumn 12, Issue 2, 2014, Pages 121-131

  Barrett, Jeffrey S ^a,b   Bajaj, Gaurav ^a   Mcguire, Jennifer ^a   Wu, Di ^a   Spitsin, Sergei ^a   Moorthy, Ganesh ^a   Zhao, Xianguo ^c   Tebas, Pablo ^b   Evans, Dwight L ^b   Douglas, Steven D ^a,b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c PharmaOn LLC   (United States)

Author keywords

Aprepitant; Clinical trial simulation; Depression; NK1R antagonism

Indexed keywords

APREPITANT; CYTOCHROME P450 3A4; PLACEBO; MORPHOLINE DERIVATIVE; NEUROKININ 1 RECEPTOR; NEUROKININ 1 RECEPTOR ANTAGONIST;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DEPRESSION; DOUBLE BLIND PROCEDURE; DRUG CLEARANCE; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIQUID CHROMATOGRAPHY; MALE; MONTE CARLO METHOD; PHASE 1 CLINICAL TRIAL; PREDICTION; RANDOMIZED CONTROLLED TRIAL; SAMPLE SIZE; TANDEM MASS SPECTROMETRY; ADOLESCENT; HIV INFECTIONS; METABOLISM; YOUNG ADULT;

ADOLESCENT; ADULT; FEMALE; HIV INFECTIONS; HUMANS; MALE; MORPHOLINES; NEUROKININ-1 RECEPTOR ANTAGONISTS; RECEPTORS, NEUROKININ-1; YOUNG ADULT;

EID: 84905644630     PISSN: 1570162X     EISSN: 18734251     Source Type: Journal    
DOI: 10.2174/1570162X12666140526120831     Document Type: Article

References (45)

1. Curran MP, Robinson DM. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs 2009; 69(13): 1853-1878.
2. Patel L, Lindley C. Aprepitant--a novel NK1-receptor antagonist. Expert Opin Pharmacother 2003; 4(12): 2279-2296.
3. Wang X, Douglas SD, Lai JP, Tuluc F, Tebas P, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) inhibits drug-resistant HIV-1 infection of macrophages in vitro. J Neuroimmune Pharmacol 2007; 2(1):42-48.
4. Wang X, Douglas SD, Song L, Wang YJ, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) suppresses HIV-1 infection of microglia/macrophages. J Neuroimmune Pharmacol 2008; 3(4): 257-264.
5. Ho WZ, Lai JP, Li Y, Douglas SD. HIV enhances substance P expression in human immune cells. FASEB J 2002; 16(6): 616-8.
6. Li Y, Douglas SD, Song L, Sun S, Ho WZ. Substance P enhances HIV-1 replication in latently infected human immune cells. J Neuroimmunol 2001; 121(1/2): 67-75.
7. Valverde EE, Purcell DW, Waldrop-Valverde D, et al. Correlates of depression among HIV-positive women and men who inject drugs. J Acquir Immune Defic Syndr 2007; 46: S96-S100.
8. Remien RH, Exner T, Kertzner RM, et al. Depressive symptomatology among HIV-positive women in the era of HAART: a stress and coping model. Am J Community Psychol 2006; 38(3/4): 275-85.
9. Kramer MS, Winokur A, Kelsey J, et al. Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression. Neuropsychopharmacology 2004; 29(2): 385-392.
10. Ranga K, Krishnan R. Clinical experience with substance P receptor (NK1) antagonists in depression. J Clin Psychiatry 2002;63 Suppl 11: 25-9.
11. Keller M, Montgomery S, Ball W, et al. Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 2006; 59(3): 216-223.
12. Barrett JS, Wu D, McGuire J, et al. Evaluation of clinical design constructs for aprepitant administration to treat HIV-associated neurocognitive disorders (HAND). Clin Pharmacol Ther 2013; 93(Suppl 1): PI-P9.
13. Hargreaves R. Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry 2002; 63(Suppl 11): 18-24.
14. Ratti E, Bettica P, Alexander R, et al. Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies. J Psychopharmacol 2013; 27(5): 424-34.
15. Barrett JS, Wu D, Moorthy G, et al. Preclinical activity predicts higher dosing requirements for the NK-1r antagonist aprepitant in HIV-associated neurocognitive disorders (HAND): Dispositional and pharmacologic rationale for multimodal therapeutic window. Clin Pharmacol Therapeut 2013; 93(Suppl 1): PI-P9.
16. Tebas P, Tuluc F, Barrett JS, et al. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults. PLoS One 2011; 6(9): e24180.
17. Ho WZ, Evans DL, Douglas SD. Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology. CNS Spectr 2002; 7(12): 867-874.
18. Geracioti TD, Jr., Carpenter LL, Owens MJ, et al. Elevated cerebrospinal fluid substance p concentrations in posttraumatic stress disorder and major depression. Am J Psychiatry 2006; 163(4): 637-43.
19. Douglas SD, Ho WZ, Gettes DR, et al. Elevated substance P levels in HIV-infected men. AIDS 2001; 15(15): 2043-5.
20. Evans DL, Ten Have TR, Douglas SD, et al. Association of depression with viral load, CD8 T lymphocytes, and natural killer cells in women with HIV infection. Am J Psychiatry 2002; 159(10): 1752-9.
21. Huskey SE, Dean BJ, Doss GA, et al. The metabolic disposition of aprepitant, a substance P receptor antagonist, in rats and dogs. Drug Metab Dispos 2004; 32(2): 246-58.
22. Sanchez RI, Wang RW, Newton DJ, et al. Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos 2004; 32(11): 1287-92.
23. EMA. EPAR scientific discussion. 2006.
24. Shadle CR, Lee Y, Majumdar AK, et al. Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol 2004; 44(3): 215-23.
25. Rost K, Fleischer F, Nieber K. Neurokinin 1 receptor antagonists-between hope and disappointment. Med Monatsschr Pharm 2006; 29(6): 200-205.
26. Majumdar AK, Howard L, Goldberg MR, et al. Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J Clin Pharmacol 2006; 46(3): 291-300.
27. Majumdar AK, McCrea JB, Panebianco DL, et al. Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. Clin Pharmacol Ther 2003; 74(2): 150-156.
28. Wu D, Paul DJ, Zhao X, Douglas SD, Barrett JS. A sensitive and rapid liquid chromatography-tandem mass spectrometry method for the quantification of the novel neurokinin-1 receptor antagonist aprepitant in rhesus macaque plasma, and cerebral spinal fluid, and human plasma with application in translational NeuroAIDs research. J Pharm Biomed Anal 2009; 49(3): 739-745.
29. Merck. Drug Approval Package: EMEND (Aprepitant) NDA #21-549. 2003.
30. German P, Warren D, West S, Hui J, Kearney BP. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV. J Acquir Immune Defic Syndr 2010; 55(3): 323-9.
31. Lepist EI, Phan TK, Roy A, et al. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother 2012;56(10):5409-13.
32. 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.
33. Moyle G. Use of HIV protease inhibitors as pharmacoenhancers. AIDS Read 2001; 11(2): 87-98; quiz 107-8.
34. Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc 2000; 75(9): 933-42.
35. Veronese ML, Gillen LP, Burke JP, et al. Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice. J Clin Pharmacol 2003; 43(8): 831-9.
36. Huskey SE, Dean BJ, Bakhtiar R, et al. Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets. Drug Metab Dispos 2003; 31(6): 785-91.
37. Nakade S, Ohno T, Kitagawa J, et al. Population pharmacokinetics of aprepitant and dexamethasone in the prevention of chemotherapy-induced nausea and vomiting. Cancer Chemother Pharmacol 2008; 63(1): 75-83.
38. Herpfer I, Lieb K. Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential. CNS Drugs 2005; 19(4): 275-93.
39. Kaplan SS, Hicks CB. Lopinavir/ritonavir in the treatment of human immunodeficiency virus infection. Expert Opin Pharmacother 2005; 6(9): 1573-85.
40. Zhang L, Zhang YD, Zhao P, Huang SM. Predicting drug-drug interactions: an FDA perspective. AAPS J 2009; 11(2): 300-6.
41. Chan-Tack K, Liu J, Jadhav P, et al. Efavirenz - rifampin interaction: Why did FDA approve efavirenz 800 mg when co-administered with rifampin? Clin Pharmacol Drug Development 2012; 1(4):198 (Abstract 1385545).
42. Manak MM, Moshkoff DA, Nguyen LT, et al. Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS 2010; 24(18): 2789-96.
43. Regoli D, Nguyen QT, Jukic D. Neurokinin receptor subtypes characterized by biological assays. Life Sci 1994; 54(26): 2035-47.
44. Lai JP, Ho WZ, Zhan GX, Yi Y, Collman RG, Douglas SD. Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc Natl Acad Sci U S A 2001; 98(7): 3970-5.
45. Kramer MS, Cutler N, Feighner J, et al. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 1998; 281(5383): 1640-5.