Pharmacokinetic-pharmacodynamic modeling of antihypertensive drugs: From basic research to clinical practice

Current Hypertension Reviews

Volumn 4, Issue 4, 2008, Pages 289-302

  Höcht, Christian ^a   Mayer, Marcos A ^a   Opezzo, Javier A W ^a   Bertera, Facundo M ^a   Taira, Carlos A ^a  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

Author keywords

Antihypertensive drugs; Clinical practice; Dose optimization; Drug development; Pharmacokinetic pharmacodynamic modeling

Indexed keywords

7 (2 ACETYLTHIO 3 PHENYLPROPIONAMIDO) 1,2,3,4,6,7,8,12B OCTAHYDRO 6 OXOPYRIDO[2,1 A][2]BENZAZEPINE 4 CARBOXYLIC ACID; ACEBUTOLOL; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIHYPERTENSIVE AGENT; BENIDIPINE; BETA 1 ADRENERGIC RECEPTOR BLOCKING AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DILTIAZEM; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DOXAZOSIN; ENALAPRIL; FELODIPINE; HYDROCHLOROTHIAZIDE; IRBESARTAN; LISINOPRIL; METHYLDOPA; METOPROLOL; MOXONIDINE; PRAZOSIN; TERAZOSIN; TRIMAZOSIN; VERAPAMIL;

ACCURACY; ANTIHYPERTENSIVE THERAPY; CALCULATION; CHEMICAL MODEL; CLINICAL PRACTICE; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENTIATION; DRUG RESEARCH; DRUG RESPONSE; DRUG SAFETY; DRUG SCREENING; DRUG SELECTIVITY; DRUG TISSUE LEVEL; GENETIC VARIABILITY; HUMAN; HYPERTENSION; NONHUMAN; PHARMACODYNAMICS; PLASMA RENIN ACTIVITY; PRIORITY JOURNAL; RELIABILITY; REVIEW; SINGLE DRUG DOSE; TREATMENT DURATION; TREATMENT RESPONSE;

EID: 58149461233     PISSN: 15734021     EISSN: None     Source Type: Journal    
DOI: 10.2174/157340208786241273     Document Type: Review

References (98)

1. Düsing R. Overcoming barriers to effective blood pressure control in patients with hypertension. Curr Med Res Opin 2006; 22: 1545-53.
2. Elliott WJ. What factors contribute to the inadequate control of elevated blood pressure? J Clin Hypertens (Greenwich) 2008; 10(1 Suppl 1): 20-6.
3. Rosskopf D, Schürks M, Rimmbach C, Schäfers R. Genetics of arterial hypertension and hypotension. Naunyn Schmiedebergs Arch Pharmacol 2007; 374: 429-69.
4. Stergiou GS. Flaws in Dose-Finding of Antihypertensive Drugs. Am J Cardiovasc Drugs 2007; 7: 357-9.
5. Derendorf H, Lesko LJ, Chaikin P, et al. Pharmacokinetic/ Pharmacodynamic modeling in drug research and development. J Clin Pharmacol 2000; 40: 1399-418.
6. Toutain PL. Pharmacokinetic/pharmacodynamic integration in drug development and dosage-regimen optimization for veterinary medicine. AAPS J 2002; 4(4):1-29.
7. Perez-Urizar j, Granados-Soto V, Flores-Murrieta FJ, Castañeda-Hernandez G. Pharmacokinetic-pharmacodynamic modeling: why? Arch Med Res 2000; 31: 539-545.
8. Dingemanse J, Appel-Dingemanse S. Integrated pharmacokinetics and pharmacodynamics in drug development. Clin Pharmacokinet 2007; 46: 713-37.
9. Balant LP, Gex-Fabry M, Balant-Gorgia E. Drug metabolism as a confounding factor in PK/PD population approaches. Therapie 1996; 51: 390-398.
10. Csajka C, Verotta D. Pharmacokinetic-pharmacodynamic modeling: history and perspectives. J. Pharmacokinet. Pharmacodyn 2006; 33: 227-279.
11. Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to D-tubocurarine. Clin Pharmacol Ther 1979; 25: 358-371.
12. Mandema JW, Tuck B, van Stevenink AL, Breimer DD, Cohen AF, Danhof M. Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite α-hydroxy-midazolam in healthy volunteers. Clin Pharmacol Ther 1992; 51: 715-728.
13. Dayneka NL, Garg V, Jusko W. Comparison of four basic models of indirect pharmacodynamic responses. J Pharmacokinet Biopharm 1993; 21: 457-78.
14. Bauer JA, Balthasar JP, Fung HL. Application of pharmacodynamic modeling for designing time-variant dosing regimens to overcome nitroglycerin tolerance in experimental heart failure. Pharm Res 1997; 14: 1140-5.
15. max-model without attaining maximal effects. J Pharmacokinet Biopharm 1998; 26: 581-93.
16. Hoffman BB. Therapy of hypertension. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGraw Hill, 2006:845-68.
17. Desai M, Stockbridge N, Temple R. Blood pressure as an example of a biomarker that functions as a surrogate. AAPS J 2006; 8: E146-52.
18. Martin C, Cameron J, McGrath B. Mechanical and circulating biomarkers in isolated clinic hypertension. Clin Exp Pharmacol Physiol 2008; 35: 402-8.
19. Mancia G, De Backer G, Dominiczak A, et al. Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 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). J Hypertens 2007; 25: 1105-87.
20. Donnelly R, Elliott HL, Meredith PA. Antihypertensive drugs: individualized analysis and clinical relevance of kinetic-dynamic relationships. Pharmacol Ther 1992; 53: 67-79.
21. Harder S, Thürmann P, Rietbrock N. Concentration/Effect Analysis of Antihypertensive Drugs. Am J Ther 1994; 1: 116-124.
22. Meredith PA. Clinical relevance of optimal pharmacokinetics in the treatment of hypertension. J Hypertens Suppl 1997; 15: S27-31.
23. Höcht C, Opezzo JAW, Bramuglia GF, Taira CA. Application of microdialysis for pharmacokinetic-pharmacodynamic modeling. Expert Opin Drug Discov 2006; 1: 289-301.
24. Harder S, Rietbrock S, Thürmann P. Concentration/effect analysis of verapamil: evaluation of different approaches. Int J Clin Pharmacol Ther Toxicol 1993; 31: 469-75.
25. Bertera FM, Mayer MA, Opezzo JAW, Taira CA, Höcht C. Comparison of different pharmacodynamic models for PK-PD modeling of verapamil in renovascular hypertension. J Pharmacol Toxicol Methods 2008; in press.
26. Bertera FM, Mayer MA, Opezzo JA, Taira CA, Bramuglia GF, Höcht C. Pharmacokinetic-pharmacodynamic modeling of diltiazem in spontaneously hypertensive rats: a microdialysis study. J Pharmacol Toxicol Methods 2007; 56: 290-9.
27. Höcht C, Di Verniero C, Opezzo JA, Bramuglia GF, Taira CA. Pharmacokinetic-pharmacodynamic (PK/PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study. Naunyn Schmiedebergs Arch Pharmacol 2006; 373: 310-8.
28. Höcht C, DiVerniero C, Opezzo JA, Taira CA. Applicability of microdialysis as a technique for pharmacokinetic-pharmacodynamic (PK/PD) modeling of antihypertensive beta-blockers. J Pharmacol Toxicol Methods 2005; 52: 244-50.
29. Höcht C, Di Verniero C, Opezzo JA, Taira CA. Pharmacokinetic-pharmacodynamic properties of metoprolol in chronic aortic coarctated rats. Naunyn Schmiedebergs Arch Pharmacol 2004; 370: 1-8.
30. Di Verniero C, Silberman EA, Mayer MA, Opezzo JAW, Taira CA, Höcht C. In Vitro and In Vivo Pharmacodynamic Properties of Metoprolol in Fructose-Fed Hypertensive Rats. J Cardiovasc Pharmacol 2008; in press.
31. Höcht C, Opezzo JA, Taira CA. Hypothalamic antihypertensive effect of metoprolol in chronic aortic coarctated rats. Clin Exp Pharmacol Physiol 2005; 32: 681-6.
32. Bellissant E, Giudicelli JF. Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients. Br J Clin Pharmacol 2001; 52: 25-33.
33. Bellissant E, Giudicelli JF. Pharmacokinetic-pharmacodynamic model relating zabiciprilat plasma concentrations to brachial and femoral haemodynamic effects in normotensive volunteers. Br J Clin Pharmacol 1998; 46: 383-93.
34. Donnelly R, Meredith PA, Elliott HL, Reid JL. Kinetic-dynamic relations and individual responses to enalapril. Hypertension 1990; 15: 301-9.
35. Aarons L, Baxter C, Gupta S. Pharmacodynamics of controlled release verapamil in patients with hypertension: an analysis using spline functions. Biopharm Drug Dispos 2004; 25: 219-25.
36. Trocóniz IF, de Alwis DP, Tillmann C, Callies S, Mitchell M, Schaefer HG. Comparison of manual versus ambulatory blood pressure measurements with pharmacokinetic-pharmacodynamic modeling of antihypertensive compounds: application to moxonidine. Clin Pharmacol Ther 2000; 68: 18-27.
37. Azizi M, Bissery A, Lamarre-Cliche M, Ménard J. Integrating drug pharmacokinetics for phenotyping individual renin response to angiotensin II blockade in humans. Hypertension 2004; 43: 785-90.
38. Hong Y, Dingemanse J, Mager D. Pharmacokinetic/Pharmacodynamic Modeling of Renin Biomarkers in Subjects Treated With the Renin Inhibitor Aliskiren. Clin Pharmacol Ther 2008; in press.
39. Elliott HL, Donnelly R, Meredith PA, Reid JL. Predictability of antihypertensive responsiveness and alpha-adrenoceptor antagonism during prazosin treatment. Clin Pharmacol Ther 1989; 46: 576-83.
40. Donnelly R, Elliott HL, Meredith PA, Reid JL. Concentration-effect relationships and individual responses to doxazosin in essential hypertension. Br J Clin Pharmacol 1989; 28: 517-26.
41. Witte DG, Brune ME, Katwala SP, et al. Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists. J Pharmacol Exp Ther 2002; 300: 495-504.
42. Vincent J, Elliott HL, Meredith PA, Reid JL. Doxazosin, an alpha 1-adrenoceptor antagonist: pharmacokinetics and concentration-effect relationships in man. Br J Clin Pharmacol 1983; 15: 719-25.
43. Campanero MA, Sádaba B, Muñoz-Juarez MJ, Quetglas EG, Azanza JR. Pharmacokinetic and pharmacodynamic modeling of arterial haemodynamic effects of terazosin in healthy volunteers. Clin Drug Investig 2008; 28: 139-47.
44. Meredith PA, Scott PJ, Kelman AW, Hughes DM, Reid JL. Effects of Age on the Pharmacokinetics and Pharmacodynamics of Cardiovascular Drugs: Application of Concentration-Effect Modeling. 3. Trimazosin. Am J Ther 1995; 2: 541-545.
45. Eliot LA, Jamali F. Pharmacokinetics and pharmacodynamics of nifedipine in untreated and atorvastatin-treated hyperlipidemic rats. J Pharmacol Exp Ther 1999; 291: 188-93.
46. Belic A, Grabnar I, Belic I, Karba R, Mrhar A. Predicting the antihypertensive effect of nitrendipine from plasma concentration profiles using artificial neural networks. Comput Biol Med 2005; 35: 892-904.
47. Ericsson H, Tholander B, Björkman JA, Nordlander M, Regårdh CG. Pharmacokinetics of new calcium channel antagonist clevidipine in the rat, rabbit, and dog and pharmacokinetic/pharmacodynamic relationship in anesthetized dogs. Drug Metab Dispos 1999; 27: 558-64.
48. Yun HY, Yun MH, Kang W, Kwon KI. Pharmacokinetics and pharmacodynamics of benidipine using a slow receptor-binding model. J Clin Pharm Ther 2005; 30:541-7.
49. Wade JR, Sambol NC. Felodipine population dose-response and concentration-response relationships in patients with essential hypertension. Clin Pharmacol Ther 1995; 57: 569-81.
50. Song JC, White CM. Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet 2002; 41: 207-24.
51. Lefebvre HP, Jeunesse E, Laroute V, Toutain PL. Pharmacokinetic and pharmacodynamic parameters of ramipril and ramiprilat in healthy dogs and dogs with reduced glomerular filtration rate. J Vet Intern Med 2006; 20: 499-507.
52. Zapater P, Novalbos J, Gallego-Sandín S, Hernández FT, Abad-Santos F. Gender differences in angiotensin-converting enzyme (ACE) activity and inhibition by enalaprilat in healthy volunteers. J Cardiovasc Pharmacol 2004; 43: 737-44.
53. Harder S, Thürmann PA, Ungethüm W. Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE-inhibitor imidapril in hypertensive patients. Br J Clin Pharmacol 1998; 45: 377-80.
54. Csajka C, Buclin T, Fattinger K, Brunner HR, Biollaz J. Population pharmacokinetic-pharmacodynamic modeling of angiotensin receptor blockade in healthy volunteers. Clin Pharmacokinet 2002; 41: 137-52.
55. Huang XH, Qiu FR, Xie HT, Li J. Pharmacokinetic and pharmacodynamic of irbesartan in renal hypertensive dogs under nonsteady-state and steady-state conditions. Eur J Drug Metab Pharmacokinet 2005; 30: 121-6.
56. Csajka C, Buclin T, Brunner HR, Biollaz J. Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists. Clin Pharmacokinet 1997; 32: 1-29.
57. Smith DH, Matzek KM, Kempthorne-Rawson J. Dose response and safety of telmisartan in patients with mild to moderate hypertension. J Clin Pharmacol 2000; 40: 1380-90.
58. Hao K, Chen YC, Cao YG, Yu D, Liu XQ, Wang GJ. Pharmacokinetic-pharmacodynamic modeling of telmisartan using an indirect response model in spontaneously hypertensive rats. Acta Pharmacol Sin 2007; 28: 738-43.
59. Meineke I, Feltkamp H, Hogemann A, Gundert-Remy U. Pharmacokinetics and pharmacodynamics of candesartan after administration of its pro-drug candesartan cilexetil in patients with mild to moderate essential hypertension - a population analysis. Eur J Clin Pharmacol 1997; 53: 221-8.
60. Wuerzner G, Azizi M. Renin inhibition with aliskiren. Clin Exp Pharmacol Physiol 2008; 35: 426-30.
61. Brockmeier D. Tight binding of ramiprilat to ACE: consequences for pharmacokinetic and pharmacodynamic measurements. Int J Clin Pharmacol Ther 1995; 33: 631-8.
62. Bellissant E, Nguyen PC, Giudicelli JF. Pharmacokinetic-pharmacodynamic model relating lisinopril plasma concentrations to regional hemodynamic effects in healthy volunteers. J Cardiovasc Pharmacol 1996; 28: 470-8.
63. Weber C, Birnböck H, Leube J, Kobrin I, Kleinbloesem CH, Van Brummelen P. Multiple dose pharmacokinetics and concentration effect relationship of the orally active renin inhibitor remikiren (Ro 42-5892) in hypertensive patients. Br J Clin Pharmacol 1993; 36: 547-54.
64. Gupta SK, Granneman GR, Packer M, Boger RS. Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a renin inhibitor). II: A dose-ranging study in patients with congestive heart failure. J Cardiovasc Pharmacol 1993; 21: 834-40.
65. van Steeg TJ, Freijer J, Danhof M, de Lange EC. Pharmacokinetic-pharmacodynamic modeling of S(-)-atenolol in rats: reduction of isoprenaline-induced tachycardia as a continuous pharmacodynamic endpoint. Br J Pharmacol 2007; 151: 356-66.
66. Baek IH, Yun MH, Yun HY, Kwon KI. Pharmacokinetic/pharmacodynamic modeling of the cardiovascular effects of beta blockers in humans. Arch Pharm Res 2008; 31: 814-21.
67. Yin XX, Zhang YD. Pharmacokinetic-pharmacodynamic modeling of metoprolol enantiomers in the dog. Yao Xue Xue Bao1997; 32: 411-5.
68. Luzier AB, Killian A, Wilton JH, Wilson MF, Forrest A, Kazierad DJ. Gender-related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Clin Pharmacol Ther 1999; 66: 594-601.
69. Scott PJ, Meredith PA, Kelman AW, Hughes DM, Reid JL. The Effects of Age on the Pharmacokinetics and Pharmacodynamics of Cardiovascular Drugs: Application of Concentration-Effect Modeling. 2. Acebutolol. Am J Ther 1995; 2: 537-540.
70. Brynne L, McNay JL, Schaefer HG, Swedberg K, Wiltse CG, Karlsson MO. Pharmacodynamic models for the cardiovascular effects of moxonidine in patients with congestive heart failure. Br J Clin Pharmacol 2001; 51: 35-43.
71. Porchet HC, Piletta P, Dayer P. Pharmacokinetic-pharmacodynamic modeling of the effects of clonidine on pain threshold, blood pressure, and salivary flow. Eur J Clin Pharmacol 1992; 42: 655-61.
72. de Visser SJ, van der Post JP, Nanhekhan L, Schoemaker RC, Cohen AF, van Gerven JM. Concentration-effect relationships of two rilmenidine single-dose infusion rates in hypertensive patients. Clin Pharmacol Ther 2002; 72: 419-28.
73. de Visser SJ, van Gerven JM, Schoemaker RC, Cohen AF. Concentration-effect relationships of two infusion rates of the imidazoline antihypertensive agent rilmenidine for blood pressure and development of side-effects in healthy subjects. Br J Clin Pharmacol 2001; 51: 423-8.
74. Lerman LO, Chade AR, Sica V, Napoli C. Animal models of hypertension: an overview. J Lab Clin Med 2005; 146: 160-73.
75. Höcht C, Opezzo JAW, Taira C. Validation of a new intraarterial microdialysis shunt probe for the estimation of pharmacokinetic parameters. J Pharm Biomed Anal 2003; 31: 1109-17.
76. Toutain PL, Lefèbvre HP. Pharmacokinetics and pharmacokinetic/ pharmacodynamic relationships for angiotensin-converting enzyme inhibitors. J Vet Pharmacol Ther 2004; 27: 515-25.
77. Blumenfeld JD. Plasma renin activity for predicting antihypertensive drug efficacy. Am J Hypertens 2008; 21: 5-6.
78. Rubattu S, Sciarretta S, Valenti V, Stanzione R, Volpe M. Natriuretic Peptides: An Update on Bioactivity, Potential Therapeutic Use, and Implication in Cardiovascular Diseases. Am J Hypertens 2008; in press.
79. Smith RE, Ashiya M. Antihypertensive therapies. Nat Rev Drug Discov 2007; 6: 597-8.
80. Cogolludo A, Pérez-Vizcaíno F, Tamargo J. New insights in the pharmacological therapy of arterial hypertension.Curr Opin Nephrol Hypertens 2005; 14: 423-7.
81. Bodineau L, Frugière A, Marc Y, Claperon C, Llorens-Cortes C. Aminopeptidase A inhibitors as centrally acting antihypertensive agents. Heart Fail Rev 2008; 13: 311-9.
82. Pfister M, Martin NE, Haskell LP, Barrett JS. Optimizing dose selection with modeling and simulation: application to the vasopeptidase inhibitor M100240. J Clin Pharmacol 2004; 44: 621-31.
83. Bühler FR, Hulthén UL, Kiowski W, Müller FB, Bolli P. The place of the calcium antagonist verapamil in antihypertensive therapy. J Cardiovasc Pharmacol 1982; 4 (Suppl 3): S350-7.
84. Ferrara LA, Fasano ML, Soro S. Age related antihypertensive effect of nitrendipine, a new calcium entry blocking agent. Eur J Clin Pharmacol 1985; 28: 473-4.
85. Resnick, L.M. Calcium metabolism, renin activity, and the antihypertensive effects of calcium channel blockade. Am J Med 1986; 15: 6-14.
86. Resnick, L.M. Calcium metabolism in the pathophysiology and treatment of clinical hypertension. Am J Hypertens 1989; 2:179S-185S.
87. Preston RA, Materson BJ, Reda DJ, Williams DW, Hamburger RJ, Cushman WC, Anderson RJ. Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. JAMA 1998; 280:1168-1172.
88. Murray L, Squire IB, Reid JL, Lees KR. Determinants of the blood pressure response to the first dose of ACE inhibitor in mild to moderate congestive heart failure. Br J Clin Pharmacol 1998; 45: 559-66.
89. Filigheddu F, Troffa C, Glorioso N. Pharmacogenomics of essential hypertension: are we going the right way? Cardiovasc Hematol Agents Med Chem 2006; 4: 7-15.
90. Mellen PB, Herrington DM. Pharmacogenomics of blood pressure response to antihypertensive treatment. J Hypertens 2005; 23: 1311-25.
91. Kurland L, Hallberg P, Melhus H, et al. The Relationship Between the Plasma Concentration of Irbesartan and the Antihypertensive Response Is Disclosed by an Angiotensin II Type 1 Receptor Polymorphism: Results From the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) Trial. Am J Hypertens 2008; in press.
92. Meredith PA, Elliott HL. Concentration-effect relationships and implications for trough-to-peak ratio. Am J Hypertens 1996; 9: 66S-70S.
93. Meredith PA, Donnelly R, Elliott HL, Howie CA, Reid JL. Prediction of the antihypertensive response to enalapril. J Hypertens 1990; 8: 1085-90.
94. Giles TD. Circadian rhythm of blood pressure and the relation to cardiovascular events. J Hypertens Suppl 2006; 24: S11-6.
95. Elliott WJ. Drug interactions and drugs that affect blood pressure. J Clin Hypertens (Greenwich) 2006; 8: 731-7.
96. Schaefer HG, Heinig R, Ahr G, Adelmann H, Tetzloff W, Kuhlmann J. Pharmacokinetic-pharmacodynamic modeling as a tool to evaluate the clinical relevance of a drug-food interaction for a nisoldipine controlled-release dosage form. Eur J Clin Pharmacol 1997; 51: 473-80.
97. Huang XH, Qiu FR, Xie HT, Li J. Pharmacokinetic and pharmacodynamic interaction between irbesartan and hydrochlorothiazide in renal hypertensive dogs. J Cardiovasc Pharmacol 2005; 46: 863-9.
98. Meredith PA, Elliott HL. An additive or synergistic drug interaction: application of concentration-effect modeling. Clin Pharmacol Ther 1992; 51: 708-14.