Hypercortisolism Caused by Ritonavir Associated Inhibition of CYP 3A4 Under Inhalative Glucocorticoid Therapy. 2 Case Reports and a Review of the Literature

C. Bernecker; T. B. West; G. Mansmann; W. A. Scherbaum; H. S. Willenberg

doi:10.1055/s-0031-1297993

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 2012; 120(03): 125-127
DOI: 10.1055/s-0031-1297993

Mini-Review

Hypercortisolism Caused by Ritonavir Associated Inhibition of CYP 3A4 Under Inhalative Glucocorticoid Therapy. 2 Case Reports and a Review of the Literature

C. Bernecker

¹Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany

,

T. B. West

²Endokrinologische Gemeinschaftspraxis am Aachener Platz, Duesseldorf, Germany

,

G. Mansmann

¹Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany

,

W. A. Scherbaum

¹Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany

,

H. S. Willenberg

¹Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany

› Institutsangaben

Abstract

Recent in vitro and in vivo studies have shown a potent inhibition of cytochrome P450 CYP3A4 through human immune deficiency virus (HIV) protease inhibitors (PIs). The PI ritonavir is described as the most potent compound within these CYP3A4 inhibitors. We present 2 cases who developed the sequelae of glucocorticoid excess following ritonavir therapy and inhalative glucocorticoid treatment: A 60-year-old HIV positive man developed the typical symptoms of Cushing’s syndrome and a 52-year-old HIV positive man developed severe osteoporosis.

Key words

adrenal - protease inhibitor - HIV - hypercortisolism - osteoporosis

Volltext

Referenzen

References
1 Aaron SD, Bishop G, Anthony J et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007; 146 (08) 545-555
2 Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med 1998; 157 (3 Pt 2) 51-53
3 Calverley PM, Anderson JA, Celli B et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356: 775-789
4 Carr A. HIV protease inhibitor-related lipodystrophy syndrome. Clin Infect Dis 2000; 30 (Suppl. 02) S135-S142
5 Chen F, Kearney T, Robinson S et al. Cushing’s syndrome and severe adrenal suppression in patients treated with ritonavir and inhaled nasal fluticasone. Sex Transm Infect 1999; 75 (04) 274
6 Dassinger M, Grohmann I, Jung B et al. Kombinationen mit beta-2Adrenorezeptor-Agonisten. In: Rote Liste, Frankfurt: Rote Liste Service GmbH 2011; 892-895
7 Drummond MB, Dasenbrook EC, Pitz MW et al. Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA 2008; 300: 2407-2416
8 Ernest 2nd CS, Hall SD, Jones DR. Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther 2005; 312: 583-591
9 Hubbard R, Tattersfield A, Smith C et al. Use of inhaled corticosteroids and the risk of fracture. Chest 2006; 130: 1082-1088
10 Hubbard RB, Smith CJ, Smeeth L et al. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002; 166 (12 Pt 1) 1563-1566
11 Johnson SR, Marion AA, Vrchoticky T et al. Cushing’s syndrome with secondary adrenal insufficiency from concomitant therapy with ritonavir and fluticasone. J Pediatr 2006; 148: 386-388
12 Kannisto S, Laatikainen A, Taivainen A et al. Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression during inhaled steroid therapy in adult asthmatic patients. Eur J Endocrinol 2004; 150: 687-690
13 Kroiss M, Quinkler M, Lutz WK et al. Drug interaction with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol 2011; 75: 585-591
14 Kumar GN, Jayanti VK, Johnson MK et al. Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans. Pharm Res 2004; 21: 1622-1630
15 Lamba JK, Lin YS, Schuetz EG et al. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002; 54: 1271-1294
16 Liu YT, Hao HP, Liu CX et al. Drugs as CYP3A probes, inducers and inhibitors. Drug Metab Rev 2007; 39: 699-721
17 Meena LP, Rai M, Singh SK et al. Endocrine changes in male HIV patients. J Assoc Physicians India 2011; 59: 365-371
18 Resmini E, Farkas C, Murillo B et al. Body composition after endogenous (Cushing’s syndrome) and exogenous (rheumatoid arthritis) exposure to glucocorticoids. Horm Metab Res 2010; 42: 613-618
19 Todd GR, Acerini CL, Ross-Russell R et al. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child 2002; 87: 457-461
20 Von Moltke LL, Greenblatt DJ, Grassi JM et al. Protease inhibitors as inhibitors of human cytochromees P450: high risk associated with ritonavir. J Clin Pharmacol 1998; 38: 106-111
21 Valin N, De Castro N, Garrait V et al. Iatrogenic Cushing’s syndrome in HIV-infected patients receiving ritonavir and inhaled fluticasone: description of 4 new cases and review of the literature. J Int Assoc Physicians AIDS Care (CHIC) 2009; 8: 113-121
22 van Erp NP, Guchelaar HJ, Ploeger BA et al. Mitotane has a strong and a durable inducing effect on CYP3A4 activity. Eur J Endocrinol 2011; 164: 621-626
23 Wainberg MA, Zaharatos GJ, Brenner BG. development of antiretroviral drug resistance. N Engl J Med 2011; 365: 637-646