Identification of the primary mechanism of action of an insulin secretagogue from meal test data in healthy volunteers based on an integrated glucose-insulin model
详细信息 查看全文
- 作者：Steve Choy (1)
Emilie Hénin (1) (2)
Jan-Stefan van der Walt (1) (3)
Maria C. Kjellsson (1)
Mats O. Karlsson (1) - 关键词：Glibenclamide ; Semi ; mechanistic ; Meal tolerance test ; Integrated glucose–insulin model ; NONMEM
- 刊名：Journal of Pharmacokinetics and Pharmacodynamics
- 出版年：2013
- 出版时间：February 2013
- 年：2013
- 卷：40
- 期：1
- 页码：1-10
- 全文大小：436KB
- 参考文献：1. Torn?e CW, Agers? H, Senderovitz T, Nielsen HA, Madsen H, Karlsson MO, Jonsson EN (2007) Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues. Br J Clin Pharmacol 63(6):648-64 CrossRef
2. Friberg LE, Karlsson MO (2003) Mechanistic models for myelosuppression. Investig New Drugs 21(2):183-94 CrossRef
3. Nielsen EI, Viberg A, L?wdin E, Cars O, Karlsson MO, Sandstr?m M (2007) Semimechanistic pharmacokinetic/pharmacodynamic model for assessment of activity of antibacterial agents from time-kill curve experiments. Antimicrob Agents Chemother 51(1):128-36 CrossRef
4. Silber HE, Jauslin PM, Frey N, Karlsson MO (2010) An integrated model for the glucose-insulin system. Basic Clin Pharmacol Toxicol 106(3):189-94 CrossRef
5. Bergman RN, Ider YZ, Bowden CR, Cobelli C (1979) Quantitative estimation of insulin sensitivity. Am J Physiol 236:E667–E677
6. De Gaetano A, Arino O (2000) Mathematical modelling of the intravenous glucose tolerance test. J Math Biol 40(2):136-68 CrossRef
7. Jauslin PM, Karlsson MO, Frey N (2011) Identification of the mechanism of action of a glucokinase activator from oral glucose tolerance test data in type 2 diabetic patients based on an integrated glucose-insulin model. J Clin Pharmacol. [Epub ahead of print] doi: 10.1177/0091270011422231 . Accessed 15 October 2012
8. Jauslin PM, Silber HE, Frey N, Gieschke R, Simonsson USH, Jorga K, Karlsson MO (2007) An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics. J Clin Pharmacol 47(10):1244-255 CrossRef
9. Silber HE, Frey N, Karlsson MO (2010) An integrated glucose-insulin model to describe oral glucose tolerance test data in healthy volunteers. J Clin Pharmacol 50(3):246-56 CrossRef
10. Silber HE, Jauslin PM, Frey N, Gieschke R, Simonsson USH, Karlsson MO (2007) An integrated model for glucose and insulin regulation in healthy volunteers and type 2 diabetic patients following intravenous glucose provocations. J Clin Pharmacol 47(9):1159-171 CrossRef
11. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368(9548):1696-705 CrossRef
12. Peart GF, Boutagy J, Shenfield GM (1989) The metabolism of glyburide in subjects of known debrisoquin phenotype. Clin Pharmacol Ther 45(3):277-84 CrossRef
13. Fuccella LM, Tamassia V, Valzelli G (1973) Metabolism and kinetics of the hypoglycemic agent glipizide in man–comparison with glibenclamide. J Clin Pharmacol New Drugs 13(2):68-5
14. Rydberg T, Wahlin-Boll E, Melander A (1991) Determination of glibenclamide and its two major metabolites in human serum and urine by column liquid chromatography. J Chromatogr 564(1):223-33 CrossRef
15. Rydberg T, J?nsson A, R?der M, Melander A (1994) Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans. Diabetes Care 17(9):1026-030 CrossRef
16. Rydberg T, Jonsson A, Melander A (1995) Comparison of the kinetics of glyburide and its active metabolites in humans. J Clin Pharm Ther 20(5):283-95 CrossRef
17. Clark CA, Gardiner J, McBurney MI, Anderson S, Weatherspoon LJ, Henry DN, Hord NG (2006) Effects of breakfast meal composition on second meal metabolic responses in adults with type 2 diabetes mellitus. Eur J Clin Nutr 60(9):1122-129 CrossRef
18. Rydberg T, J?nsson A, Karlsson MO, Melander A (1997) Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of pharmacokinetics and pharmacodynamics. Br J Clin Pharmacol 43(4):373-81 CrossRef
19. Serrano-Martín X, Payares G, Mendoza-León A (2006) Glibenclamide, a blocker of K?+?ATP channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother 50(12):4214-216 CrossRef
20. Inagaki N, Gonoi T, Clement IvJP, Wang CZ, Aguilar-Bryan L, Bryan J, Seino S (1996) A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K?+?channels. Neuron 16(5):1011-017 CrossRef
21. Ari?ns EJ, van Rossum JM, Simonis AM (1957) Affinity, intrinsic activity and drug interactions. Pharmacol Rev 9(2):218-36
22. Beal S, Sheiner LB, Boeckmann A, Bauer RJ (1989-009) NONMEM user’s guides. Icon Development Solutions, Ellicott City
23. Bergstrand M, Hooker AC, Wallin JE, Karlsson MO (2011) Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J 13(2):143-51 CrossRef
24. Liu Y, Oiki S, Tsumura T, Shimizu T, Okada Y (1998) Glibenclamide blocks volume-sensitive Cl-channels by dual mechanisms. Am J Physiol 275(2 Pt 1):C343–C351
25. Ripoll C, Lederer WJ, Nichols CG (1993) On the mechanism of inhibition of K(ATP) channels by glibenclamide in rat ventricular myocytes. J Cardiovasc Electrophysiol 4(1):38-7 CrossRef
26. Schirra J, Katschinski M, Weidmann C, Sch?fer T, Wank U, Arnold R, G?ke B (1996) Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 97(1):92-03 CrossRef
27. Collins PJ, Horowitz M, Cook DJ (1983) Gastric emptying in normal subjects—a reproducible technique using a single scintillation camera and computer system. Gut 24(12):1117-125 CrossRef
28. Creutzfeldt W (1979) The incretin concept today. Diabetologia 16(2):75-5 CrossRef
29. Holst JJ (2003) Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors. Adv Exp Med Biol 524:263-79 CrossRef
30. Nauck MA, Siemsglüss J, ?rskov C, Holst JJ (1996) Release of glucagon-like peptide 1 (GLP-1 [7-36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. Z Gastroenterol 34(3):159-66
31. Vollmer K, Hoist JJ, Bailer B, Ellrlchmann M, Nauck MA, Schmidt WE, Meier JJ (2008) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 57(3):678-87 CrossRef
32. Yamane S, Harada N, Hamasaki A, Muraoka A, Joo E, Suzuki K, Nasteska D, Tanaka D, Ogura M, Harashima SI, Inagaki N (2012) Effects of glucose and meal ingestion on incretin secretion in Japanese subjects with normal glucose tolerance. J Diabetes Invest 3(1):80-5 CrossRef
33. Pipeleers D, Kiekens R, Ling Z, Wilikens A, Schuit F (1994) Physiologic relevance of heterogeneity in the pancreatic beta-cell population. Diabetologia 37(SUPPL. 2):S57–S64 CrossRef - 作者单位：Steve Choy (1)
Emilie Hénin (1) (2)
Jan-Stefan van der Walt (1) (3)
Maria C. Kjellsson (1)
Mats O. Karlsson (1)
1. Department of Pharmaceutical Biosciences, Pharmacometrics Research Group, Uppsala University, Box 591, 751 24, Uppsala, Sweden
2. Faculté de Médecine, Université Claude Bernard Lyon 1, Lyon, France
3. Astellas Pharma Europe Ltd, Leiderdorp, The Netherlands - ISSN：1573-8744
文摘
The integrated glucose–insulin (IGI) model is a previously developed semi-mechanistic model that incorporates control mechanisms for the regulation of glucose production, insulin secretion, and glucose uptake. It has been shown to adequately describe insulin and glucose profiles in both type 2 diabetics and healthy volunteers following various glucose tolerance tests. The aim of this study was to investigate the ability of the IGI model to correctly identify the primary mechanism of action of glibenclamide (Gb), based on meal tolerance test (MTT) data in healthy volunteers. IGI models with different mechanism of drug action were applied to data from eight healthy volunteers participating in a randomized crossover study with five single-dose tests (placebo and four drug arms). The study participants were given 3.5?mg of Gb, intravenously or orally, or 3.5?mg of the two main metabolites M1 and M2 intravenously, 0.5?h prior to a standardized breakfast with energy content of 1800?kJ. Simultaneous analysis of all data by nonlinear mixed effect modeling was performed using NONMEM?. Drug effects that increased insulin secretion resulted in the best model fit, thus identifying the primary mechanism of action of Gb and metabolites as insulin secretagogues. The model also quantified the combined effect of Gb, M1 and M2 to have a fourfold maximal increase on endogenous insulin secretion, with an EC50 of 169.1?ng?mL? for Gb, 151.4?ng?mL? for M1 and 267.1?ng?mL? for M2. The semi-mechanistic IGI model was successfully applied to MTT data and identified the primary mechanism of action for Gb, quantifying its effects on glucose and insulin time profiles.