Development of a paediatric population-based model of the pharmacokinetics of rivaroxaban

Clinical Pharmacokinetics

Volumn 53, Issue 1, 2014, Pages 89-102

  Willmann, Stefan ^a   Becker, Corina ^b   Burghaus, Rolf ^b   Coboeken, Katrin ^a   Edginton, Andrea ^c   Lippert, Jörg ^a   Siegmund, Hans Ulrich ^a   Thelen, Kirstin ^a   Mück, Wolfgang ^b  

^a BAYER AG   (Germany)

^b BAYER PHARMA AG   (Germany)

^c UNIVERSITY OF WATERLOO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

RIVAROXABAN;

ADOLESCENT; ADULT; AREA UNDER THE CURVE; ARTICLE; BODY WEIGHT; CHILD; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG SAFETY; FEMALE; HUMAN; INFANT; KIDNEY CLEARANCE; LIPOPHILICITY; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRESCHOOL CHILD; PRIORITY JOURNAL; SCHOOL CHILD; TIME TO MAXIMUM PLASMA CONCENTRATION; VENOUS THROMBOEMBOLISM; YOUNG ADULT;

ADOLESCENT; ADULT; ANTICOAGULANTS; CHILD; CHILD, PRESCHOOL; FEMALE; HUMANS; INFANT; INFANT, NEWBORN; MALE; MODELS, BIOLOGICAL; MORPHOLINES; THIOPHENES;

EID: 84891885700     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-013-0090-5     Document Type: Article

References (91)

1. Raffini L, Huang YS, Witmer C, et al. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124:1001-8.
2. Goldenberg NA, Donadini MP, Kahn SR, et al. Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica. 2010;95:1952-9.
3. Kuhle S, Massicotte P, Chan A, et al. Systemic thromboembolism in children. Data from the 1-800-NO-CLOTS Consultation Service. Thromb Haemost. 2004;92:722-8.
4. Rosendaal FR. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost. 1997;78:1-6. (Pubitemid 27289208)
5. van Ommen CH, Heijboer H, Büller HR, et al. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr. 2001;139:676-81. (Pubitemid 33097433)
6. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994;83:1251-7. (Pubitemid 24062848)
7. Streif W, Ageno W. Direct thrombin and Factor Xa inhibitors in children: a quest for new anticoagulants for children. Wien Med Wochenschr. 2011;161:73-9.
8. Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e737S-801S.
9. Conroy S, McIntyre J. The use of unlicensed and off-label medicines in the neonate. Semin Fetal Neonatal Med. 2005;10:115-22. (Pubitemid 40215539)
10. Choonara I. Unlicensed and off-label drug use in children: implications for safety. Expert Opin Drug Saf. 2004;3:81-3. (Pubitemid 38765189)
11. Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. BMJ. 2000;320:79-82. (Pubitemid 30173044)
12. Cuzzolin L, Atzei A, Fanos V. Off-label and unlicensed prescribing for newborns and children in different settings: a review of the literature and a consideration about drug safety. Expert Opin Drug Saf. 2006;5:703-18. (Pubitemid 44322888)
13. 't Jong GW, Vulto AG, de Hoog M, et al. A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital. Pediatrics. 2001;108:1089-93. (Pubitemid 33021180)
14. Roberts R, Rodriguez W, Murphy D, et al. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA. 2003;290:905-11. (Pubitemid 37430462)
15. Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939 - an oral, direct Factor Xa inhibitor - after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873-80. (Pubitemid 41803696)
16. Kubitza D, Becka M, Voith B, et al. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct Factor Xa inhibitor. Clin Pharmacol Ther. 2005;78:412-21. (Pubitemid 41393676)
17. Kubitza D, Becka M, Zuehlsdorf M, et al. No interaction between the novel, oral direct Factor Xa inhibitor BAY 59-7939 and digoxin [abstract no. 11]. J Clin Pharmacol. 2006;46:702.
18. Kubitza D, Becka M, Zuehlsdorf M, et al. Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct Factor Xa inhibitor, in healthy subjects. J Clin Pharmacol. 2006;46:549-58.
19. Kubitza D, Becka M, Mueck W, et al. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban - an oral, direct Factor Xa inhibitor - are not affected by aspirin. J Clin Pharmacol. 2006;46:981-90. (Pubitemid 44215062)
20. Kubitza D, Becka M, Mueck W, et al. Rivaroxaban (BAY 59-7939) - an oral, direct Factor Xa inhibitor - has no clinically relevant interaction with naproxen. Br J Clin Pharmacol. 2007;63:469-76. (Pubitemid 46426627)
21. Kubitza D, Mueck W, Becka M. No interaction between rivaroxaban - a novel, oral, direct Factor Xa inhibitor - and atorvastatin [abstract no. P062]. Pathophysiol Haemost Thromb. 2008;36:A40.
22. Kubitza D, Becka M, Mueck W, et al. Effect of co-administration of rivaroxaban and clopidogrel on bleeding time, pharmacodynamics and pharmacokinetics: a phase I study. Pharmaceuticals. 2012;5:279-96.
23. Perzborn E, Roehrig S, Straub A, et al. The discovery and development of rivaroxaban, an oral, direct Factor Xa inhibitor. Nat Rev Drug Discov. 2011;10:61-75.
24. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765-75. (Pubitemid 351930851)
25. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372:31-9.
26. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776-86. (Pubitemid 351930852)
27. Turpie AGG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373:1673-80.
28. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499-510.
29. The EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287-97.
30. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-91.
31. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9-19.
32. Stampfuss J, Kubitza D, Becka M, et al. The effect of food on the absorption and pharmacokinetics of rivaroxaban. Int J Clin Pharmacol Ther. 2013;51:549-61.
33. Strougo A, Eissing T, Yassen A, et al. First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development. J Pharmacokinet Pharmacodyn. 2012;39:195-203.
34. Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet. 2006;45:1013-34. (Pubitemid 44436004)
35. Zhao P, Zhang L, Grillo JA, et al. Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther. 2011;89:259-67.
36. Leong R, Vieira ML, Zhao P, et al. Regulatory experience with physiologically based pharmacokinetic modeling for pediatric drug trials. Clin Pharmacol Ther. 2012;91:926-31.
37. Weinz C, Schwarz T, Kubitza D, et al. Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs and humans. Drug Metab Dispos. 2009;37:1056-64.
38. Edginton AN. Knowledge-driven approaches for the guidance of first-in-children dosing. Paediatr Anaesth. 2011;21:206-13.
39. Thelen K, Coboeken K, Willmann S, et al. Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part 1: oral solutions. J Pharm Sci. 2011;100:5324-45.
40. Thelen K, Coboeken K, Willmann S, et al. Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms. J Pharm Sci. 2012;101:1267-80.
41. Rodgers T, Leahy D, Rowland M. Physiologically based pharmacokinetic modeling 1: predicting the tissue distribution of moderate-to-strong bases. J Pharm Sci. 2005;94:1259-76. (Pubitemid 40904190)
42. Rodgers T, Rowland M. Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci. 2006;95:1238-57. (Pubitemid 43874439)
43. Rodgers T, Rowland M. Mechanistic approaches to volume of distribution predictions: understanding the processes. Pharm Res. 2007;24:918-33. (Pubitemid 46675393)
44. Kubitza D, Becka M, Mueck W, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2010;70:703-12.
45. ® (rivaroxaban) summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en-GB/document-library/ EPAR-Product-Information/human/000944/WC500057108.pdf (Accessed 22 May 2013).
46. Kubitza D, Roth A, Becka M, et al. Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban - an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2013;76:89-98.
47. Gryback P, Hermansson G, Lyrenas E, et al. Nationwide standardisation and evaluation of scintigraphic gastric emptying: reference values and comparisons between subgroups in a multicentre trial. Eur J Nucl Med. 2000;27:647-55. (Pubitemid 30408765)
48. Thelen K, Coboeken K, Jia Y, et al. Dynamically simulating the effect of food on gastric emptying using a detailed physiological model for gastrointestinal transit and absorption [abstract no. II-36]. Population Approach Group Europe, Venice; 2012.
49. Johnson KC. Dissolution and absorption modeling: model expansion to simulate the effects of precipitation, water absorption, longitudinally changing intestinal permeability, and controlled release on drug absorption. Drug Dev Ind Pharm. 2003;29:833-42. (Pubitemid 37203685)
50. Willmann S, Thelen K, Becker C, et al. Mechanism-based prediction of particle size-dependent dissolution and absorption: cilostazol pharmacokinetics in dogs. Eur J Pharm Biopharm. 2010;76:83-94.
51. Post TM, Freijer JI, Ploeger BA, et al. Extensions to the visual predictive check to facilitate model performance evaluation. J Pharmacokinet Pharmacodyn. 2008;35:185-202.
52. Bergstrand M, Hooker AC, Wallin JE, et al. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 2011;13:143-51.
53. Edginton AN, Schmitt W, Voith B, et al. A mechanistic approach for the scaling of clearance in children. Clin Pharmacokinet. 2006;45:683-704. (Pubitemid 43990570)
54. Pang KS, Rowland M. Hepatic clearance of drugs. I. Theoretical considerations of a "well-stirred" model and a "parallel tube" model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokinet Biopharm. 1977;5:625-53. (Pubitemid 8253670)
55. Edginton AN, Willmann S. Physiology-based simulations of a pathological condition: prediction of pharmacokinetics in patients with liver cirrhosis. Clin Pharmacokinet. 2008;47:743-52.
56. McNamara PJ, Alcorn J. Protein binding predictions in infants. AAPS Pharm Sci. 2002;4:E4.
57. Mahmood B, Daood MJ, Hart C, et al. Ontogeny of P-glycoprotein in mouse intestine, liver, and kidney. J Investig Med. 2001;49:250-7. (Pubitemid 32463531)
58. Rosati A, Maniori S, Decorti G, et al. Physiological regulation of P-glycoprotein, MRP1, MRP2 and cytochrome P450 3A2 during rat ontogeny. Dev Growth Differ. 2003;45:377-87. (Pubitemid 37271829)
59. Pinto N, Halachmi N, Verjee Z, et al. Ontogeny of renal P-glycoprotein expression in mice: correlation with digoxin renal clearance. Pediatr Res. 2005;58:1284-9.
60. Wagner JG. Inter- and intrasubject variation of digoxin renal clearance in normal adult males. Drug Intell Clin Pharm. 1988;22:562-7.
61. MacFarland RT, Moeller VR, Pieniaszek HJ Jr, et al. Assessment of the potential pharmacokinetic interaction between digoxin and ethmozine. J Clin Pharmacol. 1985;25:138-43. (Pubitemid 15100722)
62. Gorodischer R, Jusko WJ, Yaffe SJ. Renal clearance of digoxin in young infants. Res Commun Chem Pathol Pharmacol. 1977;16:363-74. (Pubitemid 8047052)
63. Halkin H, Radomsky M, Millman P, et al. Steady state serum concentrations and renal clearance of digoxin in neonates, infants and children. Eur J Clin Pharmacol. 1978;13:113-7. (Pubitemid 8346370)
64. Collins-Nakai RL, Schiff D, Ng PK. Multiple-dose kinetics of digoxin in neonates. Pediatr Pharmacol (New York). 1985;5:117-22. (Pubitemid 16247422)
65. Iisalo E, Dahl M. Serum levels and renal excretion of digoxin during maintenance therapy in children. Acta Paediatr Scand. 1974;63:699-704.
66. Willmann S, Lippert J, Schmitt W. From physicochemistry to absorption and distribution: predictive mechanistic modelling and computational tools. Expert Opin Drug Metab Toxicol. 2005;1:159-68.
67. Willmann S, Hohn K, Edginton A, et al. Development of a physiology-based whole-body population model for assessing the influence of individual variability on the pharmacokinetics of drugs. J Pharmacokinet Pharmacodyn. 2007;34:401-31. (Pubitemid 46873033)
68. Damkier P, Brosen K. Quinidine as a probe for CYP3A4 activity: intrasubject variability and lack of correlation with probe-based assays for CYP1A2, CYP2C9, CYP2C19, and CYP2D6. Clin Pharmacol Ther. 2000;68:199-209. (Pubitemid 30659175)
69. Gaedigk A, Baker DW, Totah RA, et al. Variability of CYP2J2 expression in human fetal tissues. J Pharmacol Exp Ther. 2006;319:523-32.
70. Rhodin MM, Anderson BJ, Peters AM, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol. 2009;24:67-76.
71. Dorne JL, Walton K, Renwick AG. Human variability in CYP3A4 metabolism and CYP3A4-related uncertainty factors for risk assessment. Food Chem Toxicol. 2003;41:201-24. (Pubitemid 35447872)
72. Sy SK, Ciaccia A, Li W, et al. Modeling of human hepatic CYP3A4 enzyme kinetics, protein, and mRNA indicates deviation from log-normal distribution in CYP3A4 gene expression. Eur J Clin Pharmacol. 2002;58:357-65. (Pubitemid 34983927)
73. Garzi A, Messina M, Frati F, et al. An extensively hydrolysed cow's milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants. Allergol Immunopathol (Madr). 2002;30:36-41.
74. Shaaban SY, Nassar MF, Sawaby AS, et al. Ultrasonographic gastric emptying in protein energy malnutrition: effect of type of meal and nutritional recovery. Eur J Clin Nutr. 2004;58:972-8. (Pubitemid 38923197)
75. Vivatvakin B, Buachum V. Effect of carob bean on gastric emptying time in Thai infants. Asia Pac J Clin Nutr. 2003;12:193-7. (Pubitemid 38886751)
76. Fallingborg J, Christensen LA, Ingeman-Nielsen M, et al. Measurement of gastrointestinal pH and regional transit times in normal children. J Pediatr Gastroenterol Nutr. 1990;11:211-4. (Pubitemid 20225906)
77. Ofori-Kwakye K, Fell JT, Sharma HL, et al. Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release. Int J Pharm. 2004;270:307-13. (Pubitemid 38077110)
78. Hoekstra JH. Fructose breath hydrogen tests in infants with chronic non-specific diarrhoea. Eur J Pediatr. 1995;154:362-4.
79. Khin M, Bolin TD, Tin O, et al. Investigation of small-intestinal transit time in normal and malnourished children. J Gastroenterol. 1999;34:675-9.
80. Soares AC, Lederman HM, Fagundes-Neto U, et al. Breath hydrogen test after a bean meal demonstrates delayed oro-cecal transit time in children with chronic constipation. J Pediatr Gastroenterol Nutr. 2005;41:221-4. (Pubitemid 41102243)
81. Van Den Driessche M, Van Malderen N, Geypens B, et al. Lactose-[13C]ureide breath test: a new, noninvasive technique to determine orocecal transit time in children. J Pediatr Gastroenterol Nutr. 2000;31:433-8.
82. Vreugdenhil G, Sinaasappel M, Bouquet J. A comparative study of the mouth to caecum transit time in children and adults using a weight adapted lactulose dose. Acta Paediatr Scand. 1986;75:483-8. (Pubitemid 16064156)
83. Madsen JL. Effects of gender, age, and body mass index on gastrointestinal transit times. Dig Dis Sci. 1992;37:1548-53.
84. Wagener S, Shankar KR, Turnock RR, et al. Colonic transit time - what is normal? J Pediatr Surg. 2004;39:166-9. (Pubitemid 38146430)
85. Helander HF. Quantitative morphological methods in intestinal research. Scand J Gastroenterol Suppl. 1985;112:1-5. (Pubitemid 15029596)
86. Willmann S, Edginton AN, Kleine-Besten M, et al. Whole-body physiologically based pharmacokinetic population modelling of oral drug administration: inter-individual variability of cimetidine absorption. J Pharm Pharmacol. 2009;61:891-9.
87. Wilding I, Hirst P, Connor A. Development of a new engineering-based capsule for human drug absorption studies. Pharm Sci Technol Today. 2000;3:385-92.
88. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). General considerations for pediatric pharmacokinetic studies for drugs and biological products; 1998. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm072114.pdf (Accessed 19 Mar 2013).
89. Mueck W, Borris LC, Dahl OE, et al. Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Haemost. 2008;100:453-61.
90. Mueck W, Becka M, Kubitza D, et al. Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban - an oral, direct Factor Xa inhibitor - in healthy subjects. Int J Clin Pharmacol Ther. 2007;45:335-44. (Pubitemid 46895052)
91. Mueck W, Lensing AW, Agnelli G, et al. Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet. 2011;50:675-86.