A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin, pioglitazone and fenofibrate in healthy subjects^*

References

• Wood JM, Maibaum J, Rahuel J, et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun 2003;308:698–7051. Wood JM, Maibaum J, Rahuel J, et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun 2003;308:698–705
   PubMed Web of Science ®Google Scholar
• Nussberger J, Wuerzner G, Jensen C, et al. Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension 2002;39:E1–82. Nussberger J, Wuerzner G, Jensen C, et al. Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension 2002;39:E1–8
   PubMed Web of Science ®Google Scholar
• Tekturna. US prescribing information. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 20073. Tekturna. US prescribing information. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 2007
   Google Scholar
• Rasilez. EU summary of product characteristics. Novartis Europharm Ltd, Horsham, W Sussex, UK, 20074. Rasilez. EU summary of product characteristics. Novartis Europharm Ltd, Horsham, W Sussex, UK, 2007
   Google Scholar
• Gradman AH, Schmieder RE, Lins RL, et al. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005;111:1012–85. Gradman AH, Schmieder RE, Lins RL, et al. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005;111:1012–8
   PubMed Web of Science ®Google Scholar
• Kushiro T, Itakura H, Abo Y, et al. Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension. Hypertens Res 2006;29:997–10056. Kushiro T, Itakura H, Abo Y, et al. Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension. Hypertens Res 2006;29:997–1005
   PubMed Web of Science ®Google Scholar
• Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007;49:1157–637. Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007;49:1157–63
   PubMed Web of Science ®Google Scholar
• Pool JL, Gradman AH, Kolloch R, et al. Aliskiren, a novel renin inhibitor, provides long-term suppression of the renin system, when used alone or in combination with hydrochlorothiazide in the treatment of hypertension. Eur Heart J 2006;27 Suppl:119 P-7908. Pool JL, Gradman AH, Kolloch R, et al. Aliskiren, a novel renin inhibitor, provides long-term suppression of the renin system, when used alone or in combination with hydrochlorothiazide in the treatment of hypertension. Eur Heart J 2006;27 Suppl:119 P-790
   Google Scholar
• Schmieder RE, Philipp T, Guerediaga J, et al. Aliskiren-based therapy lowers blood pressure more effectively than hydrochlorothiazide-based therapy in patients with hypertension. J Clin Hypertens 2007;9 Suppl A:A182 P-4369. Schmieder RE, Philipp T, Guerediaga J, et al. Aliskiren-based therapy lowers blood pressure more effectively than hydrochlorothiazide-based therapy in patients with hypertension. J Clin Hypertens 2007;9 Suppl A:A182 P-436
   Google Scholar
• Selby JV, Peng T, Karter AJ, et al. High rates of co-occurrence of hypertension, elevated low-density lipoprotein cholesterol, and diabetes mellitus in a large managed care population. Am J Manag Care 2004;10:163–7010. Selby JV, Peng T, Karter AJ, et al. High rates of co-occurrence of hypertension, elevated low-density lipoprotein cholesterol, and diabetes mellitus in a large managed care population. Am J Manag Care 2004;10:163–70
   PubMed Web of Science ®Google Scholar
• Weycker D, Nichols GA, O'Keeffe-Rosetti M, et al. Risk-factor clustering and cardiovascular disease risk in hypertensive patients. Am J Hypertens 2007;20:599–60711. Weycker D, Nichols GA, O'Keeffe-Rosetti M, et al. Risk-factor clustering and cardiovascular disease risk in hypertensive patients. Am J Hypertens 2007;20:599–607
   PubMed Web of Science ®Google Scholar
• Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560–7212. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560–72
   PubMed Web of Science ®Google Scholar
• Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007;28:1462–53613. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007;28:1462–536
   PubMed Web of Science ®Google Scholar
• Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006;29:1963–7214. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006;29:1963–72
   PubMed Web of Science ®Google Scholar
• Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007;30:162–7215. Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007;30:162–72
   PubMed Web of Science ®Google Scholar
• Uresin Y, Taylor A, Kilo C, et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst 2007;8:190–816. Uresin Y, Taylor A, Kilo C, et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst 2007;8:190–8
   PubMed Web of Science ®Google Scholar
• Waldmeier F, Glaenzel U, Wirz B, et al. Absorption, distribution, metabolism, and elimination of the direct renin inhibitor aliskiren in healthy volunteers. Drug Metab Dispos 2007;35:1418–2817. Waldmeier F, Glaenzel U, Wirz B, et al. Absorption, distribution, metabolism, and elimination of the direct renin inhibitor aliskiren in healthy volunteers. Drug Metab Dispos 2007;35:1418–28
   PubMed Web of Science ®Google Scholar
• Vaidyanathan S, Bigler H, Yeh C, et al. Pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with irbesartan in renal impairment. Clin Pharmacokinet 2007;46:661–7518. Vaidyanathan S, Bigler H, Yeh C, et al. Pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with irbesartan in renal impairment. Clin Pharmacokinet 2007;46:661–75
   PubMed Web of Science ®Google Scholar
• Vaidyanathan S, Warren V, Yeh C, et al. Pharmacokinetics, safety, and tolerability of the oral renin inhibitor aliskiren in patients with hepatic impairment. J Clin Pharmacol 2007;47:192–20019. Vaidyanathan S, Warren V, Yeh C, et al. Pharmacokinetics, safety, and tolerability of the oral renin inhibitor aliskiren in patients with hepatic impairment. J Clin Pharmacol 2007;47:192–200
   PubMed Web of Science ®Google Scholar
• Dieterich H-A, Kemp C, Vaidyanathan S, et al. Aliskiren, the first in a new class of orally effective renin inhibitors, has no clinically significant drug interactions with digoxin in healthy volunteers. Clin Pharmacol Ther 2007;79:PIII-2420. Dieterich H-A, Kemp C, Vaidyanathan S, et al. Aliskiren, the first in a new class of orally effective renin inhibitors, has no clinically significant drug interactions with digoxin in healthy volunteers. Clin Pharmacol Ther 2007;79:PIII-24
   Web of Science ®Google Scholar
• Dieterle W, Corynen S, Mann J. Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects. Br J Clin Pharmacol 2004;58:433–621. Dieterle W, Corynen S, Mann J. Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects. Br J Clin Pharmacol 2004;58:433–6
   PubMed Web of Science ®Google Scholar
• Dieterle W, Corynen S, Vaidyanathan S, et al. Pharmacokinetic interactions of the oral renin inhibitor aliskiren with lovastatin, atenolol, celecoxib and cimetidine. Int J Clin Pharmacol Ther 2005;43:527–3522. Dieterle W, Corynen S, Vaidyanathan S, et al. Pharmacokinetic interactions of the oral renin inhibitor aliskiren with lovastatin, atenolol, celecoxib and cimetidine. Int J Clin Pharmacol Ther 2005;43:527–35
   PubMed Web of Science ®Google Scholar
• Vaidyanathan S, Valencia J, Kemp C, et al. Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. Int J Clin Pract 2006;60:1343–5623. Vaidyanathan S, Valencia J, Kemp C, et al. Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. Int J Clin Pract 2006;60:1343–56
   PubMed Web of Science ®Google Scholar
• Kiser JJ, Gerber JG, Predhomme JA, et al. Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr 2008;47:570–824. Kiser JJ, Gerber JG, Predhomme JA, et al. Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr 2008;47:570–8
   PubMed Web of Science ®Google Scholar
• Zhao C, Vaidyanathan S, Yeh CM, et al. Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with type 2 diabetes mellitus. Clin Pharmacokinet 2006;45:1125–3425. Zhao C, Vaidyanathan S, Yeh CM, et al. Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with type 2 diabetes mellitus. Clin Pharmacokinet 2006;45:1125–34
   PubMed Web of Science ®Google Scholar
• Metropolitan height and weight tables. Stat Bull Metrop Life Found 1983;64:3–926. Metropolitan height and weight tables. Stat Bull Metrop Life Found 1983;64:3–9
   PubMedGoogle Scholar
• Zhong WZ, Williams MG. Simultaneous quantitation of pioglitazone and its metabolites in human serum by liquid chromatography and solid phase extraction. J Pharm Biomed Anal 1996;14:465–7327. Zhong WZ, Williams MG. Simultaneous quantitation of pioglitazone and its metabolites in human serum by liquid chromatography and solid phase extraction. J Pharm Biomed Anal 1996;14:465–73
   PubMed Web of Science ®Google Scholar
• Guidance for Industry: In vivo drug metabolism/drug interaction studies – study design, data analysis, and recommendations for dosing and labeling: FDA/Center for Drug Evaluation and Research; 200128. Guidance for Industry: In vivo drug metabolism/drug interaction studies – study design, data analysis, and recommendations for dosing and labeling: FDA/Center for Drug Evaluation and Research; 2001
   Google Scholar
• Bailey CJ. Metformin – an update. Gen Pharmacol 1993;24:1299–30929. Bailey CJ. Metformin – an update. Gen Pharmacol 1993;24:1299–309
   PubMedGoogle Scholar
• Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf 2005;28:601–3130. Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf 2005;28:601–31
   PubMed Web of Science ®Google Scholar
• Davidson MB, Peters AL. An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med 1997;102:99–11031. Davidson MB, Peters AL. An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med 1997;102:99–110
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996;30:359–7132. Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996;30:359–71
   PubMed Web of Science ®Google Scholar
• Elte JW, Blickle JF. Thiazolidinediones for the treatment of type 2 diabetes. Eur J Intern Med 2007;18:18–2533. Elte JW, Blickle JF. Thiazolidinediones for the treatment of type 2 diabetes. Eur J Intern Med 2007;18:18–25
   PubMed Web of Science ®Google Scholar
• Budde K, Neumayer HH, Fritsche L, et al. The pharmacokinetics of pioglitazone in patients with impaired renal function. Br J Clin Pharmacol 2003;55:368–7434. Budde K, Neumayer HH, Fritsche L, et al. The pharmacokinetics of pioglitazone in patients with impaired renal function. Br J Clin Pharmacol 2003;55:368–74
   PubMed Web of Science ®Google Scholar
• Azizi M, Webb R, Nussberger J, et al. Renin inhibition with aliskiren: where are we now, and where are we going?. J Hypertens 2006;24:243–5635. Azizi M, Webb R, Nussberger J, et al. Renin inhibition with aliskiren: where are we now, and where are we going?. J Hypertens 2006;24:243–56
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacokinetic interactions with thiazolidinediones. Clin Pharmacokinet 2007;46:1–1236. Scheen AJ. Pharmacokinetic interactions with thiazolidinediones. Clin Pharmacokinet 2007;46:1–12
   PubMed Web of Science ®Google Scholar
• Jaakkola T, Laitila J, Neuvonen PJ, et al. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol 2006;99:44–5137. Jaakkola T, Laitila J, Neuvonen PJ, et al. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol 2006;99:44–51
   PubMed Web of Science ®Google Scholar
• Vaidyanathan S, Jin Y, Schiller H, et al. Aliskiren, a novel oral renin inhibitor, has no interaction with cytochrome P450 isoenzymes in vitro. Basic Res Pharmacol Toxicol 2005;97:23938. Vaidyanathan S, Jin Y, Schiller H, et al. Aliskiren, a novel oral renin inhibitor, has no interaction with cytochrome P450 isoenzymes in vitro. Basic Res Pharmacol Toxicol 2005;97:239
   Google Scholar
• Vaidyanathan S, Jarugula V, Dieterich H-A, et al. Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet 2008 [in press]39. Vaidyanathan S, Jarugula V, Dieterich H-A, et al. Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet 2008 [in press]
   PubMedGoogle Scholar
• Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005;54:2460–7040. Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005;54:2460–70
   PubMed Web of Science ®Google Scholar
• Miller DB, Spence JD. Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet 1998;34:155–6241. Miller DB, Spence JD. Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet 1998;34:155–62
   PubMed Web of Science ®Google Scholar
• Ehrhardt M, Lindenmaier H, Burhenne J, et al. Influence of lipid lowering fibrates on p-glycoprotein activity in vitro. Biochem Pharmacol 2004;67:285–9242. Ehrhardt M, Lindenmaier H, Burhenne J, et al. Influence of lipid lowering fibrates on p-glycoprotein activity in vitro. Biochem Pharmacol 2004;67:285–92
   PubMed Web of Science ®Google Scholar
• Vaidyanathan S, Reynolds C, Yeh C-M, et al. The pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with the p-glycoprotein modulators ketoconazole, digoxin and atorvastatin in healthy subjects. Clin Pharmacol Ther 2007;81 Suppl 1:S109 PIII-7543. Vaidyanathan S, Reynolds C, Yeh C-M, et al. The pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with the p-glycoprotein modulators ketoconazole, digoxin and atorvastatin in healthy subjects. Clin Pharmacol Ther 2007;81 Suppl 1:S109 PIII-75
   Web of Science ®Google Scholar
• Rautio J, Humphreys JE, Webster LO, et al. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos 2006;34:786–9244. Rautio J, Humphreys JE, Webster LO, et al. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos 2006;34:786–92
   PubMed Web of Science ®Google Scholar
• Ayalasomayajula S, Tchaloyan S, Yeh C-M, et al. A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with allopurinol, celecoxib and cimetidine in healthy subjects. Curr Med Res Opin 2008;24:717–2645. Ayalasomayajula S, Tchaloyan S, Yeh C-M, et al. A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with allopurinol, celecoxib and cimetidine in healthy subjects. Curr Med Res Opin 2008;24:717–26
   PubMed Web of Science ®Google Scholar
• Howlett HC, Bailey CJ. A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999;20:489–50346. Howlett HC, Bailey CJ. A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999;20:489–503
   PubMed Web of Science ®Google Scholar
• Fullert S, Schneider F, Haak E, et al. Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 2002;87:5503–647. Fullert S, Schneider F, Haak E, et al. Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 2002;87:5503–6
   PubMed Web of Science ®Google Scholar
• Dormandy J, Charbonnel B, Eckland D, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279–8948. Dormandy J, Charbonnel B, Eckland D, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279–89
   PubMed Web of Science ®Google Scholar
• Lincoff A, Wolski K, Nicholls S, et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 2007;298:1180–849. Lincoff A, Wolski K, Nicholls S, et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 2007;298:1180–8
   PubMed Web of Science ®Google Scholar