Propionyl l-carnitine: Intermittent claudication and peripheral arterial disease

Expert Opinion on Pharmacotherapy

Volumn 10, Issue 16, 2009, Pages 2697-2707

  Andreozzi, G M ^a  

^a UNIVERSITY HOSPITAL OF PADOVA   (Italy)

Author keywords

Intermittent claudication; Management of intermittent claudication; Peripheral arterial disease; Physical training in intermittent claudication

Indexed keywords

CILOSTAZOL; DROMOS; NAFTIDROFURYL; PLACEBO; PROPIONYLCARNITINE; UNCLASSIFIED DRUG;

ARTERY DISEASE; CLINICAL TRIAL; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ELIMINATION; HEMODYNAMICS; HUMAN; INTERMITTENT CLAUDICATION; OXIDATIVE STRESS; PHARMACODYNAMICS; QUALITY OF LIFE; REVIEW; TRAINING; WALKING;

CARDIOTONIC AGENTS; CARNITINE; EXERCISE; HUMANS; INTERMITTENT CLAUDICATION; PERIPHERAL VASCULAR DISEASES;

EID: 72949123705     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656560903215871     Document Type: Review

References (79)

1. Andreozzi GM, Arosio E, Martini R, et al. Consensus document on intermittent claudication from the Central European Vascular Forum 1st edition - Abano Terme (Italy) - May 2005 2nd revision - Portroz (Slovenia) September 2007. Int Angiol 2008;27(2):93-113
2. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation 1995;91(5):1472-1479
3. Brevetti G, Martone VD, Perna S, et al. Intermittent claudication and risk of cardiovascular events. Angiology 1998;49(10):843-848
4. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326(6):381-386
5. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286(11):1317-1324
6. Jelnes R, Gaardsting O, Hougaard Jensen K, et al. Fate in intermittent claudication: outcome and risk factors. Br Med J 1986;293(6555):1137-1140
7. O'Riordain DS, O'Donnell JA. Realistic expectations for the patient with intermittent claudication. Br J Surg 1991;78(7):861-863
8. Rosenbloom MS, Flanigan DP, Schuler JJ, et al. Risk factors affecting the natural history of intermittent claudication. Arch Surg 1988;123(7):867-870
9. Andreozzi GM, Martini R. The fate of the claudicant limb. Eur Heart J 2002;4(Suppl B):B41-5
10. Wilson SE, Schwartz I, Williams RA, Owens ML. Occlusion of the superficial femoral artery: what happens without operation. Am J Surg 1980;140(1):112-118
11. Dormandy JA, Murray GD. The fate of the claudicant-a prospective study of 1969 claudicants. Eur J Vasc Surg 1991;5(2):131-133
12. Girolami B, Bernardi E, Prins MH, et al. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. Arch Intern Med 1999;159(4):337-345
13. Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Database Syst Rev 2000;(2):CD000990
14. Wind J, Koelemay MJ. Exercise therapy and the additional effect of supervision on exercise therapy in patients with intermittent claudication. Systematic review of randomised controlled trials. Eur J Vasc Endovasc Surg 2007;34(1):1-9
15. Hiatt WR, Regensteiner JG, Hargarten ME, et al. Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation 1990;81(2):602-609
16. Hiatt WR, Wolfel EE, Meier RH, Regensteiner JG. Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response. Circulation 1994;90(4):1866-1874
17. Andreozzi GM, Signorelli SS, Tornetta D. The rehabilitation of angiology. Amsterdam: Elsevier, 1990
18. Gardner AW, Killewich LA, Montgomery PS, Katzel LI. Response to exercise rehabilitation in smoking and nonsmoking patients with intermittent claudication. J Vasc Surg 2004;39(3):531-538
19. Ubels FL, Links TP, Sluiter WJ, et al. Walking training for intermittent claudication in diabetes. Diabetes Care 1999;22(2):198-201
20. Leone A, Laudani R, Definite G, et al. Unbalanced risk factors, could compromise the effectiveness of physical training in patients with intermittent claudication? Minerva Cardioangiol 2009;57(2):165-174
21. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg 2007;33(Suppl 1):S1-75 (Pubitemid 46068992)
22. Hirsch AT, Haskal ZJ, Hertzer NR. ACC/AHA Guidelines for the management of PAD. J Am Coll Cardiol 2006;20(10):1-75
23. Stewart KJ, Hiatt WR, Regensteiner JG, Hirsch AT. Exercise training for claudication. N Engl J Med 2002;347(24):1941-1951
24. Andreozzi GM, Martini R, Cordova R, et al. Circulating levels of cytokines (IL-6 and IL-1beta) in patients with intermittent claudication, at rest, after maximal exercise treadmill test and during restore phase. Could they be progression markers of the disease? Int Angiol 2007;26(3):245-252
25. Brevetti G, Martone VD, de Cristofaro T, et al. High levels of adhesion molecules are associated with impaired endothelium-dependent vasodilation in patients with peripheral arterial disease. Thromb Haemost 2001;85(1):63-66
26. Cordova R, Martini R, D'Eri A, et al. Flogistic arterial activity or own inflammatory attitude: what acts on PAD evolution? Int J Angiol 2003;22(Suppl 1):21-22
27. Hickman P, Harrison DK, Hill A, et al. Exercise in patients with intermittent claudication results in the generation of oxygen derived free radicals and endothelial damage. Adv Exp Med Biol 1994;361:565-570
28. Signorelli SS, Mazzarino MC, Di Pino L, et al. High circulating levels of cytokines (IL-6 and TNFalpha), adhesion molecules (VCAM-1 and ICAM-1) and selectins in patients with peripheral arterial disease at rest and after a treadmill test. Vasc Med 2003;8(1):15-19
29. Tisi PV, Shearman CP. The evidence for exercise-induced inflammation in intermittent claudication: should we encourage patients to stop walking? Eur J Vasc Endovasc Surg 1998;15(1):7-17
30. Andreozzi GM, Leone A, Martini R, et al. Effectiveness and costs of a short-course supervised training program in claudicants: proposal for a shared protocol with aerobic working load. Int Angiol 2008;27(5):401-407
31. Andreozzi GM. Terapia medica delle ischemie croniche degli arti inferiori. Torino: Minerva Medica, 2001
32. Pagnan A, Lusiani L, Visona A, Ferrari M. Terapia medica delle arteropatie obliteranti degli arti inferiori. 4th edition. Padova: Piccin, 20
33. Debakey ME, Burch G, Ray T, Ochsner A. The "Borrowing-lending" hemodynamic phenomenon (hemometakinesia) and its therapeutic application in peripheral vascular disturbances. Ann Surg 1947;126(6):850-865
34. Regensteiner JG, Wolfel EE, Brass EP, et al. Chronic changes in skeletal muscle histology and function in peripheral arterial disease. Circulation 1993;87(2):413-421
35. Marconi C, Ferretti G, Anchisi S, et al. Energetics of walking in patients with peripheral arterial disease: a proposed functional evaluation protocol. Clin Sci (Lond) 2003;105(1):105-111
36. Pipinos II, Sharov VG, Shepard AD, et al. Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease. J Vasc Surg 2003;38(4):827-832
37. Hiatt WR. Carnitine and peripheral arterial disease. Ann NY Acad Sci 2004;1033:92-98
38. Taylor DJ, Amato A, Hands LJ, et al. Changes in energy metabolism of calf muscle in patients with intermittent claudication assessed by 31P magnetic resonance spectroscopy: a phase II open study. Vasc Med 1996;1(4):241-245
39. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003;42(11):941-967
40. Wiseman LR, Brogden RN. Propionyl-L-carnitine. Drugs Aging 1998;12(3):243-8; discussion 9-50
41. Capecchi PL, Laghi Pasini F, Quartarolo E, Di Perri T. Carnitines increase plasma levels of adenosine and ATP in humans. Vasc Med 1997;2(2):77-81
42. Amico-Roxas M, Caruso A, Cutuli VM, et al. Inhibitory effects of propionyl-L-carnitine on plasma extravasation induced by irritants in rodents. Drugs Exp Clin Res 1993;19(5):213-217
43. Bertelli A, Giovannini L, Galmozzi G, Bertelli AA. Protective role of propionyl carnitine in vascular disorders experimentally induced by endothelin (ET-1) serotonin and K-carrageenin. Drugs Exp Clin Res 1993;19(1):7-11
44. Bertelli A, Bertelli AA, Galmozzi G, et al. Thrombosis induced by endothelin (ET-1) and carrageenin in rats treated with indomethacin and propionyl carnitine. Drugs Exp Clin Res 1993;19(2):75-78
45. Cevese A, Schena F, Poltronieri R, Cerutti G. Short term effects of intra-arterial propionyl-L-carnitine on isolated canine hind-limbs. Cardioscience 1995;6(1):59-64
46. Corsico N, Nardone A, Lucreziotti MR, et al. Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study. Cardiovasc Drugs Ther 1993;7(2):241-251
47. Brevetti G, Angelini C, Rosa M, et al. Muscle carnitine deficiency in patients with severe peripheral vascular disease. Circulation 1991;84(4):1490-1495
48. Cipolla MJ, Nicoloff A, Rebello T, et al. Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism. J Vasc Surg 1999;29(6):1097-1103
49. Triggiani M, Oriente A, Golino P, et al. Inhibition of platelet-activating factor synthesis in human neutrophils and platelets by propionyl-L-carnitine. Biochem Pharmacol 1999;58(8):1341-1348
50. Brevetti G, Fanin M, De Amicis V, et al. Changes in skeletal muscle histology and metabolism in patients undergoing exercise deconditioning: effect of propionyl-L-carnitine. Muscle Nerve 1997;20(9):1115-1120
51. Signorelli SS, Malaponte G, Di Pino L, et al. Effects of ischemic stress on leukocyte activation processes in patients with chronic peripheral occlusive arterial disease: role of L-propionyl carnitine administration. Pharmacol Res 2001;44(4):305-309
52. Silvestro A, Schiano V, Bucur R, et al. Effect of propionylcarnitine on changes in endothelial function and plasma levels of adhesion molecules induced by acute exercise in patients with intermittent claudication. Angiology 2006;57(2):145-154
53. Andreozzi GM, Martini R, Cordova RM, D'Eri A. L-propionyl-carnitine protects tissues from ischemic injury in an 'in vivo' human ischemia-reperfusion model. Clin Drug Invest 2002;22(Suppl 1):15-21
54. Signorelli SS, Fatuzzo P, Rapisarda F, et al. A randomised, controlled clinical trial evaluating changes in therapeutic efficacy and oxidative parameters after treatment with propionyl L-carnitine in patients with peripheral arterial disease requiring haemodialysis. Drugs Aging 2006;23(3):263-270
55. Hiatt WR, Regensteiner JG, Creager MA, et al. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med 2001;110(8):616-622
56. Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol 1999;34(5):1618-1624
57. Brevetti G, Perna S, Sabba C, et al. Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol 1995;26(6):1411-1416
58. Coto V, D'Alessandro L, Grattarola G, et al. Evaluation of the therapeutic efficacy and tolerability of levocarnitine propionyl in the treatment of chronic obstructive arteriopathies of the lower extremities: a multicentre controlled study vs. placebo. Drugs Exp Clin Res 1992;18(1):29-36
59. Santo SS, Sergio N, Luigi DP, et al. Effect of PLC on functional parameters and oxidative profile in type 2 diabetes-associated PAD. Diabetes Res Clin Pract 2006;72(3):231-237
60. Allegra C, Antignani PL, Schachter I, et al. Propionyl-L-carnitine in Leriche-Fontaine stage II peripheral arterial obstructive disease. Ann Vasc Surg 2008;22(4):552-558
61. Dal Lago A, De Martini D, Flore R, et al. Effects of propionyl-L- carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial. Drugs Exp Clin Res 1999;25(1):29-36
62. Ragozzino G, Mattera E, Madrid E, et al. Effects of propionyl-carnitine in patients with type 2 diabetes and peripheral vascular disease: results of a pilot trial. Drugs R D 2004;5(4):185-190
63. Strano A. Propionyl-L-carnitine versus pentoxifylline: improvement in walking capacity in patients with intermittent claudication. Clin Drug Invest 2002;22(Suppl 1):1-6
64. Andreozzi GM, Leone A, Laudani R, et al. Levo-propionyl-carnitine improves the effectiveness of supervised physical training on the absolute claudication distance in patients with intermittent claudication. Angiology 2008;59(1):84-89
65. Greco AV, Mingrone G, Bianchi M, Ghirlanda G. Effect of propionyl-L-carnitine in the treatment of diabetic angiopathy: controlled double blind trial versus placebo. Drugs Exp Clin Res 1992;18(2):69-80
66. Andreozzi GM, Leone A, Laudani R, et al. Acute impairment of the endothelial function by maximal treadmill exercise in patients with intermittent claudication, and its improvement after supervised physical training. Int Angiol 2007;26(1):12-17
67. Packer L, Valenza M, Serbinova E, et al. Free radical scavenging is involved in the protective effect of L-propionyl-carnitine against ischemia-reperfusion injury of the heart. Arch Biochem Biophys 1991;288(2):533-537
68. Reznick AZ, Kagan VE, Ramsey R, et al. Antiradical effects in L-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. Arch Biochem Biophys 1992;296(2):394-401
69. Vanella A, Russo A, Acquaviva R, et al. L -propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol 2000;16(2):99-104
70. Stroh R, Christopher TA, Lopez BL, et al. L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti-shock and endothelial protective effects in rat splanchnic ischemia-reperfusion injury. Shock 1998;9(3):216-222
71. Pignatelli P, Lenti L, Sanguigni V, et al. Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress. Am J Physiol Heart Circ Physiol 2003;284(1):H41-8
72. Loffredo L, Marcoccia A, Pignatelli P, et al. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J 2007;28(5):608-612
73. Brevetti G, Perna S, Sabba C, et al. Effect of propionyl-L-carnitine on quality of life in intermittent claudication. Am J Cardiol 1997;79(6):777-780
74. The TASC working Group. Management of peripheral arterial disease (PAD). Trans Atlantic Inter-Society Consensus (TASC). Int Angiol 2000;19(1 Suppl 1):I-XXIV, 1-304
75. EMEA. Reflection paper on the regulatory guidance for the use of Health-Related Quality of Life (HRQL) measures in the evaluation of medicinal products. 2005; Available from: http://www.emea.europa.eu/ [Cited]
76. Signorelli SS, Di Pino L, Costa MP, et al. Efficacy of L-propionyl carnitine in the treatment of chronic critical limb ischaemia. Clin Drug Invest 2001;21(8):555-561
77. Persico G, Amato B, Aprea G, et al. The early effects of intravenous L-propionyl carnitine on ulcerative trophic lesions of the lower limbs in arteriopathic patients: a controlled randomized study. Drugs Exp Clin Res 1995;21(5):187-198
78. Pola P, Flore R, Serricchio M, Tondi P. New carnitine derivatives for the therapy of cutaneous ulcers in vasculopathics. Drugs Exp Clin Res 1991;17(5):277-282
79. Milio G, Novo G, Genova G, et al. Pharmacological treatment of patients with chronic critical limb ischemia: L-propionyl-carnitine enhances the short-term effects of PGE-1. Cardiovasc Drugs Ther 2009. [Epub ahead of print]