Drug effects on the CVS in conscious rats: Separating cardiac output into heart rate and stroke volume using PKPD modelling

British Journal of Pharmacology

Volumn 171, Issue 22, 2014, Pages 5076-5092

  Snelder, N ^a   Ploeger, B A ^a   Luttringer, O ^b   Rigel, D F ^c   Fu, F ^c   Beil, M ^c   Stanski, D R ^b   Danhof, M ^a,d  

^a LEIDEN UNIVERSITY   (Netherlands)

^b NOVARTIS PHARMA AG   (Switzerland)

^c NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^d LEIDEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMILORIDE; AMLODIPINE; ATROPINE; ENALAPRIL; FASUDIL; HYDROCHLOROTHIAZIDE; PRAZOSIN; PROPRANOLOL; 1 (5 ISOQUINOLINESULFONYL) 2 METHYLPIPERAZINE;

ANIMAL EXPERIMENT; ARTERY CATHETER; ARTICLE; ASCENDING AORTA; BLOOD FLOW; CIRCADIAN RHYTHM; DRUG MECHANISM; HEART OUTPUT; HEART RATE; HEART STROKE VOLUME; MALE; MEAN ARTERIAL PRESSURE; NEGATIVE FEEDBACK; NONHUMAN; QUANTITATIVE ANALYSIS; RAT; SPONTANEOUSLY HYPERTENSIVE RAT; WISTAR KYOTO RAT; ANALOGS AND DERIVATIVES; ANIMAL; BIOLOGICAL MODEL; DRUG EFFECTS; HEMODYNAMICS; HYPERTENSION; METABOLISM;

1-(5-ISOQUINOLINESULFONYL)-2-METHYLPIPERAZINE; AMILORIDE; AMLODIPINE; ANIMALS; ATROPINE; ENALAPRIL; HEMODYNAMICS; HYDROCHLOROTHIAZIDE; HYPERTENSION; MALE; MODELS, BIOLOGICAL; PRAZOSIN; PROPRANOLOL; RATS, INBRED SHR; RATS, INBRED WKY;

EID: 84915790897     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12824     Document Type: Article

References (43)

1. Anderson BJ, Holford NH (2009). Mechanistic basis of using body size and maturation to predict clearance in humans. Drug Metab Pharmacokinet 24: 25-36.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL et al. (2013). The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors. Br J Pharmacol 170: 1459-1581.
3. Asdaq SM, Inamdar MN (2009). The potential for interaction of hydrochlorothiazide with garlic in rats. Chem Biol Interact 181: 472-479.
4. Belpaire FM, de Smet F, Vynckier LJ, Vermeulen AM, Rosseel MT, Bogaert MG et al. (1990). Effect of aging on the pharmacokinetics of atenolol, metoprolol and propranolol in the rat. J Pharmacol Exp Ther 254: 116-122.
5. Cardinale D, Bacchiani G, Beggiato M, Colombo A, Cipolla CM (2013). Strategies to prevent and treat cardiovascular risk in cancer patients. Semin Oncol 40: 186-198.
6. Cleophas TJ (1998). Mechanisms offsetting the beneficial effects of antihypertensive drugs: a problem increasingly considered but incompletely understood. Am J Ther 5: 413-419.
7. Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X et al. (2010). Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362: 402-415.
8. Danhof M, de Jongh J, De Lange EC, Della Pasqua O, Ploeger BA, Voskuyl RA (2007). Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis. Annu Rev Pharmacol Toxicol 47: 357-400.
9. Danhof M, de Lange EC, Della Pasqua OE, Ploeger BA, Voskuyl RA (2008). Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research. Trends Pharmacol Sci 29: 186-191.
10. Dayneka NL, Garg V, Jusko WJ (1993). Comparison of four basic models of indirect pharmacodynamic responses. J Pharmacokinet Biopharm 21: 457-478.
11. Doursout MF, Wouters P, Kashimoto S, Hartley CJ, Rabinovitz R, Chelly JE (2001). Measurement of cardiac function in conscious rats. Ultrasound Med Biol 27: 195-202.
12. Ebadi M (2008). Desk Reference of Clinical Pharmacology. Taylor & Francis Group: Boca Raton, FL.
13. Francheteau P, Steimer JL, Merdjan H, Guerret M, Dubray C (1993). A mathematical model for dynamics of cardiovascular drug action: application to intravenous dihydropyridines in healthy volunteers. J Pharmacokinet Biopharm 21: 489-514.
14. Frohlich ED (1989). Angiotensin converting enzyme inhibitors. Present and future. Hypertension 13: I125-I130.
15. Gasparyan AY, Ayvazyan L, Cocco G, Kitas GD (2012). Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research. Curr Pharm Des 18: 1543-1555.
16. Guth BD (2007). Preclinical cardiovascular risk assessment in modern drug development. Toxicol Sci 97: 4-20.
17. Hamilton CA, Reid JL, Vincent J (1985). Pharmacokinetic and pharmacodynamic studies with two alpha-adrenoceptor antagonists, doxazosin and prazosin in the rabbit. Br J Pharmacol 86: 79-87.
18. Hong Y, Dingemanse J, Mager DE (2008). Pharmacokinetic/pharmacodynamic modeling of renin biomarkers in subjects treated with the renin inhibitor aliskiren. Clin Pharmacol Ther 84: 136-143.
19. Ikegaki I, Hattori T, Yamaguchi T, Sasaki Y, Satoh SI, Asano T et al. (2001). Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats. Eur J Pharmacol 427: 69-75.
20. Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH et al. (2006). Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 355: 1124-1140.
21. Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P et al. (2010). A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362: 387-401.
22. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010). NC3Rs Reporting Guidelines Working Group. Br J Pharmacol 160: 1577-1579.
23. Levick JR (2003). An Introduction to Cardiovascular Physiology. Hodder Arnold Publishers: London.
24. Li P, Callery PS, Gan LS, Balani SK (2007). Esterase inhibition attribute of grapefruit juice leading to a new drug interaction. Drug Metab Dispos 35: 1023-1031.
25. Lin JH, Chen IW, Ulm EH, Duggan DE (1988). Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats. Drug Metab Dispos 16: 392-396.
26. Louis WJ, Howes LG (1990). Genealogy of the spontaneously hypertensive rat and Wistar-Kyoto rat strains: implications for studies of inherited hypertension. J Cardiovasc Pharmacol 16: S1-S5.
27. Masumoto A, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A (2001). Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension 38: 1307-1310.
28. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
29. Michalewicz L, Messerli FH (1997). Cardiac effects of calcium antagonists in systemic hypertension. Am J Cardiol 79: 39-46.
30. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucl Acids Res 42 (Database Issue): D1098-D1106.
31. Perez-Reyes E, Van Deusen AL, Vitko I (2009). Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther 328: 621-627.
32. Perlstein I, Stepensky D, Krzyzanski W, Hoffman A (2002). A signal transduction pharmacodynamic model of the kinetics of the parasympathomimetic activity of low-dose scopolamine and atropine in rats. J Pharm Sci 91: 2500-2510.
33. Pinto YM, Paul M, Ganten D (1998). Lessons from rat models of hypertension: from Goldblatt to genetic engineering. Cardiovasc Res 39: 77-88.
34. Ploeger BA, van der Graaf PH, Danhof M (2009). Incorporating receptor theory in mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling. Drug Metab Pharmacokinet 24: 3-15.
35. Reid JL, Elliott HL, Vincent J, Meredith PA (1987). Clinical pharmacology of selective alpha blockers. Hemodynamics and effects on lipid levels. Am J Med 82: 15-20.
36. Segre G, Cerretani D, Bruni G, Urso R, Giorgi G (1998). Amiloride pharmacokinetics in rat. Eur J Drug Metab Pharmacokinet 23: 218-222.
37. Snelder N, Ploeger BA, Luttringer O, Rigel DF, Webb RL, Feldman D et al. (2013a). PKPD modeling of the interrelationship between mean arterial blood pressure, cardiac output and total peripheral resistance in conscious rats. Br J Pharmacol 169: 1510-1524.
38. Snelder N, Ploeger BA, Luttringer O, Rigel DF, Webb RL, Feldman D et al. (2013b). Mechanism-based PKPD modeling of cardiovascular effects in conscious rats - an applicatyion to fingolimod. Population Approach Group Europe (PAGE) 22. Abstract 2686 Available at: http://www.page-meeting.org/?abstract=2686 (accessed 6/13/2013).
39. van Steeg TJ, Krekels EH, Freijer J, Danhof M, de Lange EC (2010). Effect of altered AGP plasma binding on heart rate changes by S(-)-propranolol in rats using mechanism-based estimations of in vivo receptor affinity (K(B,vivo)). J Pharm Sci 99: 2511-2520.
40. Stopher DA, Beresford AP, Macrae PV, Humphrey MJ (1988). The metabolism and pharmacokinetics of amlodipine in humans and animals. J Cardiovasc Pharmacol 12: S55-S59.
41. Sudano I, Flammer AJ, Roas S, Enseleit F, Noll G, Ruschitzka F (2012). Nonsteroidal antiinflammatory drugs, acetaminophen, and hypertension. Curr Hypertens Rep 14: 304-309.
42. Visser SA, Sallstrom B, Forsberg T, Peletier LA, Gabrielsson J (2006). Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats. J Pharmacol Exp Ther 317: 209-219.
43. West GB, Brown JH, Enquist BJ (1999). The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science 284: 1677-1679.