Evaluation of the effect of fluconazole and ketoconazole on the pharmacokinetics of tofacitinib in healthy adult subjects

Clinical Pharmacology in Drug Development

Volumn 3, Issue 1, 2014, Pages 72-77

  Gupta, Pankaj ^a   Chow, Vincent ^a   Wang, Ronnie ^a   Kaplan, Irina ^a   Chan, Gary ^a   Alvey, Christine ^a   Ni, Grace ^a   Ndongo, Marie Noella ^a   Labadie, Robert R ^a   Krishnaswami, Sriram ^a  

^a PFIZER INC   (United States)

Author keywords

Cytochrome P450; Drug drug interactions; Fluconazole; Ketoconazole; Tofacitinib

Indexed keywords

FLUCONAZOLE; KETOCONAZOLE; TOFACITINIB;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG EXPOSURE; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; DRUG SCREENING; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; LOADING DRUG DOSE; MALE; MIGRAINE; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION;

EID: 84892463284     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1002/cpdd.71     Document Type: Article

References (13)

1. Meyer DM, Jesson MI, Li X, et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690, 550, in rat adjuvant-induced arthritis. J Inflamm. 2010; 7:41.
2. Coombs JH, Bloom BJ, Breedveld FC, et al. Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690, 550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2010; 69:413-416.
3. Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dose levels of CP-690, 550 versus placebo. Arthritis Rheum. 2009; 60:1895-1905.
4. Boy MG, Wang C, Wilkinson BE, et al. Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690, 550 in patients with psoriasis. J Invest Dermatol. 2009; 129:2299-2302.
5. Busque S, Leventhal J, Brennan DC, et al. Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690, 550: a pilot study in de novo kidney allograft recipients. Am J Transplant. 2009; 9:1936-1945.
6. Prakash C, Lin J, Chan G, Boy M. Metabolism, pharmacokinetics and excretion of a Janus kinase-3 inhibitor, CP-690, 550, in healthy male volunteers. AAPS J. 2008; 10:2492A.
7. Riese RJ, Krishnaswami S, Kremer J. Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes. Best Pract Res Clin Rheumatol. 2010; 24:513-5526.
8. Gupta P, Alvey C, Wang R, et al. Lack of effect of tofacitinib (CP-690, 550) on the pharmacokinetics of the CYP3A4 substrate midazolam in healthy volunteers: confirmation of in vitro data. Br J Clin Pharmacol. 2012; 74:109-115.
9. Krishnaswami S, Kudlacz E, Yocum S, et al. Effect of CYP2C19 polymorphism on the pharmacokinetics of CP-690, 550, a Janus kinase inhibitor [abstract]. AAPS J. 2009; 11:36A [Abstract 36].
10. Thummel KE, Wilkinson GR. In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol. 1998; 38:389-430.
11. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin Pharmacokinet. 2000; 38:111-180.
12. Lamba M, Wang R, Stock T, O'Gorman M, Krishnaswami S. The effect of food on the pharmacokinetics of tofacitinib (CP-690, 550) [abstract]. Clin Pharmacol Ther. 2012; 91:S35 [Abstract PI-74].
13. Gupta P, Stock T, Wang R, Alvey C, Choo H, Krishnaswami S. A Phase 1 study to estimate the absolute oral bioavailability of tofacitinib (CP-690, 550) in healthy subjects [abstract]. Abstract 1-12-1122902 presented at the American College of Clinical Pharmacology-40th Annual Meeting, 2011.