Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin

Journal of Diabetes Science and Technology

Volumn 8, Issue 4, 2014, Pages 821-829

  De La Peña, Amparo ^a   Ma, Xiaosu ^a   Reddy, Shobha ^a   Ovalle, Fernando ^b   Bergenstal, Richard M ^c   Jackson, Jeffrey A ^d  

^a ELI LILLY AND COMPANY   (United States)

^b UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

^c INTERNATIONAL DIABETES CENTER   (United States)

^d Lilly USA ^*  (United States)

Author keywords

Dosing; Modeling; Pharmacodynamics; Pharmacokinetics; Simulation; Time action profile; U 500 regular human insulin

Indexed keywords

ANTIDIABETIC AGENT; INSULIN;

ADULT; ALGORITHM; CLINICAL TRIAL; COMPUTER SIMULATION; CROSSOVER PROCEDURE; DIABETES MELLITUS; DOSE RESPONSE; DRUG ADMINISTRATION; FEMALE; GLUCOSE CLAMP TECHNIQUE; HUMAN; MALE; METABOLISM; OBESITY; REPRODUCIBILITY; STATISTICAL MODEL;

ADULT; ALGORITHMS; COMPUTER SIMULATION; CROSS-OVER STUDIES; DIABETES MELLITUS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; GLUCOSE CLAMP TECHNIQUE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; MALE; MODELS, STATISTICAL; OBESITY; REPRODUCIBILITY OF RESULTS;

EID: 84905924940     PISSN: None     EISSN: 19322968     Source Type: Journal    
DOI: 10.1177/1932296814532326     Document Type: Article

References (33)

1. Humulin R® U-500 [product label]. Indianapolis, IN: Eli Lilly and Company; 2013.
2. Reutrakul S, Wroblewski K, Brown RL. Clinical use of U-500 regular insulin: review and meta-analysis. J Diabetes Sci Technol. 2012;6:412-20.
3. NIH Clinical Trials Study Record Detail. U.S. National Institutes of Health website. Available at: http://clinicaltrials.gov/ct2/show/NCT01774968. NLM Identifier: NCT01774968. Accessed July 21, 2013.
4. IMS Health National Prescription Audit Monthly, January 2007-August 2010. Data on file. Indianapolis, IN: Eli Lilly and Company.
5. Galloway JA, Spradlin CT, Nelson RL, Wentworth SM, Davidson JA, Swarner JL. Factors influencing the absorption, serum insulin concentration, and blood glucose responses after injections of regular insulin and various insulin mixtures. Diabetes Care. 1981;4:366-376.
6. Davidson MB, Navar MD, Echeverry D, Duran P. U-500 regular insulin: clinical experience and pharmacokinetics in obese, severely insulin-resistant type 2 diabetic patients. Diabetes Care. 2010;33:281-283.
7. de la Peña A, Riddle M, Morrow LA, et al. Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care. 2011;34:2496-2501.
8. Binder C. Absorption of injected insulin. A clinical-pharmacological study. Acta Pharmacol Toxicol (Copenh). 1969;27(suppl 2):1-84.
9. Jorgensen KH, Hansen AK, Buschard K. Fivefold increase in insulin concentration delays the absorption of subcutaneous injected human insulin suspensions in pigs. Diabetes Res Clin Pract. 2000;50:161-167.
10. Ovalle F. Clinical approach to the patient with diabetes mellitus and very high insulin requirements. Diabetes Res Clin Pract. 2010;90:231-242.
11. Lane WS, Cochran EK, Jackson JA, et al. High-dose insulin therapy: is it time for U-500 insulin? Endocr Pract. 2009;15: 71-79.
12. Segal AR, Brunner JE, Burch FT, Jackson JA. Use of concentrated insulin human regular (U-500) for patients with diabetes. Am J Health-Sys Pharm. 2010;67:1526-1535.
13. Cochran EK, Valentine V, Samaan K, Corey IB, Jackson JA. U-500 regular insulin therapy in high-dose insulin-requiring patients with diabetes: what diabetes educators need to know. Diabetes Educator. 2005;28:1240-1244. http://tde.sagepub.com/cgi/content/abstract/0145721713508822v1?papetoc.
14. Quinn SL, Lansang C, Mina D. Safety and effectiveness of U-500 insulin therapy in patients with insulin-resistant type 2 diabetes mellitus. Pharmacotherapy. 2011;31:695-702.
15. Landersdorfer CB, Jusko WJ. Pharmacokinetic/pharmacodynamic modeling of glucose clamp effects of inhaled and subcutaneous insulin in healthy volunteers and diabetic patients. Drug Metab Pharmacokinet. 2010;25(5):418-429.
16. Potocka E, Baughman RA, Derendorf H. Population pharmacokinetic model of human insulin following different routes of administration. J Clin Pharmacol. 2011;51:1015-1024.
17. Ballani P, Tran MT, Navar MD, Davidson MB. Clinical experience with U-500 regular insulin in obese, markedly insulin-resistant type 2 diabetic patients. Diabetes Care. 2006;29:2504-2505. Erratum 2007;30:455.
18. Ziesmer AE, Kelly KC, Guerra PA, George KG, Dunn FL. U-500 Regular insulin use in insulin resistant type 2 diabetic veteran patients. Endocr Pract. 2012;18:34-38.
19. Neal JM. Analysis of effectiveness of human U-500 insulin in patients unresponsive to conventional insulin therapy. Endocr Pract. 2005;11:305-307.
20. Wafa WS, Khan MI. Use of U-500 regular insulin in type 2 diabetes. Diabetes Care. 2006;29:2175-2176.
21. Dailey AM, Williams S, Taneja D, Tannock LR. Clinical efficacy and patient satisfaction with U-500 insulin use. Diabetes Res Clin Pract. 2010;88:259-264.
22. Garg R, Lawrence IG, Akinsola MO, Davies MJ, McNally PG. Improved glycaemic control in severely insulin resistant, insulin-treated diabetic patients with U500 Human Actrapid over two year follow-up [abstract]. Diabetologia. 2004;47(suppl 1):A58.
23. Nayyar V, Jarvis J, Lawrence I, et al. Long-term followup of patients U-500 insulin: a case series. Pract Diab Int. 2010;27:194-197.
24. Boldo A, Comi RJ. Clinical experience with U500 insulin: risks and benefits. Endocr Pract. 2012;18:56-61.
25. Lowery JB, Donihi AC, Korytkowski MT. U-500 insulin as a component of basal bolus insulin therapy in type 2 diabetes. Diabetes Technol Ther. 2012;14:505-507.
26. Cochran E, Musso C, Gorden P. The use of U-500 in patients with extreme insulin resistance. Diabetes Care. 2005;28:1240-1244.
27. Garg R, Johnston V, McNally PG, Davies MJ, Lawrence IG. U-500 insulin: why, when and how to use in clinical practice. Diabetes Metab Res Rev. 2007;23:265-268.
28. Cochran E. U-500 insulin: when more with less yields success. Diabetes Spectr. 2009;22:116-121.
29. Cochran E, Gorden P. Use of U-500 insulin in the treatment of severe insulin resistance. Insulin. 2008;3:211-218.
30. Woodworth JR, Howey DC, Bowsher RR. Establishment of time-action profiles for regular and NPH insulin using pharmacodynamics modeling. Diabetes Care. 1994;17(1):64-69.
31. Woodworth JR, Howey DC, Bowsher RR, Lutz S, Santa PF, Brady P. [Lys(B28), Pro(B29)] human insulin (K): dose-ranging vs. Humulin R (H) [abstract]. Diabetes. 1993;42(suppl 1):54A.
32. Trajanoski Z, Wach P, Kotanko P, Ott A, Skraba F. Pharmacokinetic model for the absorption of subcutaneously injected soluble insulin and monomeric insulin analogues. Biomed Tech (Berl). 1993;38:224-231.
33. Gagnon-Auger M, du Souich P, Baillargeon JP, et al. Dosedependent delay of the hypoglycemic effect of short-acting insulin analogs in obese subjects with type 2 diabetes: a pharmacokinetic and pharmacodynamic study. Diabetes Care. 2010;33:2502-2507.