Clinical Pharmacokinetic and Pharmacodynamic Profile of Idelalisib

Clinical Pharmacokinetics

Volumn 55, Issue 1, 2016, Pages 33-45

  Ramanathan, Srinivasan ^a   Jin, Feng ^a   Sharma, Shringi ^a   Kearney, Brian P ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE OXIDASE; BREAST CANCER RESISTANCE PROTEIN; CYTOCHROME P450 3A; DRUG METABOLITE; GS 563117; IDELALISIB; KETOCONAZOLE; MIDAZOLAM; MULTIDRUG RESISTANCE PROTEIN; RIFAMPICIN; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B3; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; PURINE DERIVATIVE; QUINAZOLINONE DERIVATIVE;

AREA UNDER THE CURVE; CHRONIC LYMPHATIC LEUKEMIA; DIARRHEA; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG METABOLISM; DRUG SAFETY; FOLLICULAR LYMPHOMA; HUMAN; INFECTION; LEUKEMIA RELAPSE; MODERATE HEPATIC IMPAIRMENT; NEUTROPENIA; PHARMACODYNAMIC PARAMETERS; PHARMACOKINETIC PARAMETERS; PNEUMONIA; PRIORITY JOURNAL; RASH; REVIEW; SEVERE HEPATIC IMPAIRMENT; SIDE EFFECT; VOLUME OF DISTRIBUTION; DOSE RESPONSE; DRUG INTERACTION; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOMA, NON-HODGKIN; METABOLISM; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; ANTINEOPLASTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOMA, NON-HODGKIN; PURINES; QUINAZOLINONES;

EID: 84954375294     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-015-0304-0     Document Type: Review

References (37)

1. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol. 1997;7(4):261–9.
2. Bader AG, Kang S, Zhao L, Vogt PK. Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer. 2005;5(12):921–9.
3. Clayton E, Bardi G, Bell SE, Chantry D, Downes CP, Gray A, et al. A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J Exp Med. 2002;196(6):753–63.
4. Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003;3(4):317–30.
5. Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC. Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem Sci. 2005;30(4):194–204.
6. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol. 2010;11(5):329–41.
7. Bernal A, Pastore RD, Asgary Z, Keller SA, Cesarman E, Liou HC, et al. Survival of leukemic B cells promoted by engagement of the antigen receptor. Blood. 2001;98(10):3050–7.
8. Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 1997;275(5300):661–5.
9. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193–204.
10. Shukla S, Maclennan GT, Hartman DJ, Fu P, Resnick MI, Gupta S. Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer. 2007;121(7):1424–32.
11. Herman SE, Lapalombella R, Gordon AL, Ramanunni A, Blum KA, Jones J, et al. The role of phosphatidylinositol 3-kinase-delta in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemia. Blood. 2011;117(16):4323–7.
12. Hoellenriegel J, Meadows SA, Sivina M, Wierda WG, Kantarjian H, Keating MJ, et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118(13):3603–12.
13. Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117(2):591–4.
14. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, et al. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–18.
15. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007.
16. Sharman JP, Coutre SE, Furman RR, Cheson BD, Pagel JM, Hillmen P, et al. Second interim analysis of phase 3 study of idelalisib plus rituximab for relapsed CLL: efficacy analysis in patient subpopulations with del(17p) and other adverse prognostic factors. Blood. 2014;124(21):330.
17. ®) in combination with bendamustine (B), bendamustine/rituximab (BR), fludarabine (F), chlorambucil (Chl), or chlorambucil/rituximab (ChlR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Blood. 2014;124(21):3343.
18. Somoza JR, Koditek D, Villasenor AG, Novikov N, Wong MH, Liclican A, et al. Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase delta. J Biol Chem. 2015;290(13):8439–46.
19. Herman SE, Johnson AJ. Molecular pathways: targeting phosphoinositide 3-kinase p110-delta in chronic lymphocytic leukemia. Clin Cancer Res. 2012;18(15):4013–8.
20. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015;94(3):193–205.
21. Vanhaesebroeck B, Khwaja A. PI3Kdelta inhibition hits a sensitive spot in B cell malignancies. Cancer Cell. 2014;25(3):269–71.
22. Yang Q, Modi P, Ramanathan S, Quéva C, Gandhi V. Idelalisib for the treatment of B-cell malignancies. Expert Opinion Orphan Drugs. 2015;3(1):109–23.
23. Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014;123(22):3390–7.
24. Webb HK, Chen H, Yu AS, Peterman S, Holes L, Lannutti B, et al. Clinical pharmacokinetics of CAL-101, a p110δ isoform-selective PI3K inhibitor, following single- and multiple-dose administration in healthy volunteers and patients with hematological malignancies. ASH Annual Meeting Abstracts. 2010;116(21):1774.
25. Jin F, Zhou H, Fang L, Li X, Newcomb T, Dansey R, et al. Exposure–response of idelalisib, a novel PI3Kδ inhibitor, in the treatment of hematologic malignancies. Blood. 2013;122(21):5054.
26. Jin F, Gao Y, Zhou H. Population pharmacokinetic modeling of idelalisib, a novel PI3Kδ inhibitor, in healthy subjects and patients with hematologic malignancies. J Pharmacokinet Pharmacodyn. 2014;41:S69.
27. Jin F, Robeson M, Zhou H, Kwan E, Ramanathan S. Pharmacokinetics, metabolism and excretion of idelalisib. Blood. 2013;122(21):5570.
28. Chen H, Evarts J, Webb H, Ulrich R. Biotransformation of GS-1101 (CAL-101), a potent and selective inhibitor of PI3K delta for the treatment of patients with hematologic malignancies. FASEB J. 2012;26:850.
29. Jin F, Zhou H, Gao Y, Li X, Newcomb T, Ramanathan S. Effect of intrinsic and extrinsic factors on pharmacokinetics of idelalisib, a novel PI3Kδ inhibitor, in patients with hematologic malignancies. Clin Pharmacol Ther. 2015;97(Suppl 1):S84.
30. Jin F, Robeson M, Zhou H, Hisoire G, Ramanathan S. The pharmacokinetics and safety of idelalisib in subjects with moderate or severe hepatic impairment. J Clin Pharmacol. 2015. doi:10.1002/jcph.504(Epub 2015 Mar 27).
31. Garattini E, Terao M. The role of aldehyde oxidase in drug metabolism. Expert Opin Drug Metab Toxicol. 2012;8(4):487–503.
32. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human phase I metabolizing enzymes except for cytochrome P450 and phase II metabolizing enzymes. Drug Metab Pharmacokinet. 2006;21(5):357–74.
33. Jin F, Robeson M, Zhou H, Hisoire G, Ramanathan S. The pharmacokinetics and safety of idelalisib in subjects with severe renal impairment. Blood. 2013;122(21):5572.
34. Jin F, Robeson M, Zhou H, Moyer C, Wilbert S, Murray B, et al. Clinical drug interaction profile of idelalisib in healthy subjects. J Clin Pharmacol. 2015. doi:10.1002/jcph.495(Epub 2015 Mar 11).
35. Fenner KS, Troutman MD, Kempshall S, Cook JA, Ware JA, Smith DA, et al. Drug–drug interactions mediated through P-glycoprotein: clinical relevance and in vitro–in vivo correlation using digoxin as a probe drug. Clin Pharmacol Ther. 2009;85(2):173–81.
36. Dixit V, Hariparsad N, Li F, Desai P, Thummel KE, Unadkat JD. Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human hepatocytes: implications for predicting clinical drug interactions. Drug Metab Dispos. 2007;35(10):1853–9.
37. Jin F, Sharma S, Zhou H, Gao Y, Li X, Newcomb T, et al. Effect of acid reducing agents on the pharmacokinetics of idelalisib, a novel PI3Kδ inhibitor, in patients with hematologic malignancies. Clin Pharmacol Ther. 2015;97(Suppl 1):S83.