Population pharmacokinetics of telapristone (CDB-4124) and its active monodemethylated metabolite CDB-4453, with a mixture model for total clearance

AAPS Journal

Volumn 13, Issue 4, 2011, Pages 665-673

  Morris, Denise ^a   Podolski, Joseph ^b   Kirsch, Alan ^b   Wiehle, Ronald ^b   Fleckenstein, Lawrence ^a  

^a UNIVERSITY OF IOWA   (United States)

^b Repros Therapeutics   (United States)

Author keywords

CDB 4453; mixture model; parent metabolite; population pharmacokinetics; telapristone (CDB 4124)

Indexed keywords

CDB 4453; CYTOCHROME P450 3A5; DRUG METABOLITE; TELAPRISTONE; TELAPRISTONE ACETATE; UNCLASSIFIED DRUG;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; COMPARTMENT MODEL; CONTROLLED STUDY; DISTRIBUTION VOLUME; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG METABOLISM; DRUG SAFETY; ENZYME POLYMORPHISM; FEMALE; HUMAN; KIDNEY FAILURE; KIDNEY INJURY; KINETICS; LIVER FAILURE; MATHEMATICAL ANALYSIS; MAXIMUM PLASMA CONCENTRATION; NONLINEAR SYSTEM; OPEN STUDY; PARALLEL DESIGN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADULT; AREA UNDER CURVE; HUMANS; MIDDLE AGED; MODELS, BIOLOGICAL; NORPREGNADIENES;

EID: 83555166144     PISSN: 15507416     EISSN: None     Source Type: Journal    
DOI: 10.1208/s12248-011-9304-7     Document Type: Article

References (30)

1. GR Jang LZ Benet 1997 Antiprogestin pharmacodynamics, pharmacokinetics, and metabolism: implications for their long-term use J Pharmacokinet Biopharm 25 6 647 672 9697076 10.1023/A:1025725716343 1:CAS:528:DyaK1cXlt1ersLw%3D (Pubitemid 28358089)
2. G Neef S Beier W Elger D Henderson R Wiechert 1984 New steroids with antiprogestational and antiglucocorticoid activities Steroids 44 4 349 372 6152725 10.1016/S0039-128X(84)80027-6 1:CAS:528:DyaL28XjsVagsg%3D%3D (Pubitemid 15015372)
3. Contraceptive and Reproductive Health Branch, NICHD, Report to the National Advisory Child Health and Human Development Council. http://www.nichd.nih.gov/publications/pubs/upload/CRHB-council-report-June-2008. pdf. Updated 2008. Accessed September, 2010.
4. RD Wiehle J Goldberg T Brodniewicz K Jarus-Dziedzic Z Jabiry-Zieniewicz 2008 Effects of a new progesterone receptor modulator, CDB-4124, on fibroid size and uterine bleeding US Obstet Gynecol 3 17 20
5. BJ Attardi J Burgenson SA Hild JR Reel RP Blye 2002 CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914 Mol Cell Endocrinol 188 1-2 111 123 11911951 10.1016/S0303-7207(01) 00743-2 1:CAS:528:DC%2BD38XitFWntrg%3D (Pubitemid 34242671)
6. BJ Attardi J Burgenson SA Hild JR Reel 2004 In vitro antiprogestational/ antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone J Steroid Biochem Mol Biol 88 3 277 288 15120421 10.1016/j.jsbmb.2003.12.004 1:CAS:528:DC%2BD2cXjs1eru7k%3D (Pubitemid 38553759)
7. IM Spitz 2009 Clinical utility of progesterone receptor modulators and their effect on the endometrium Curr Opin Obstet Gynecol 21 4 318 324 19602929 10.1097/GCO.0b013e32832e07e8
8. Spitz I.M., Wiehle R.D., van As A. Progesterone receptor modulators in endometriosis: A new therepeutic option. In: Gracia-Valesco J, Rizk B,RMB., eds. Endometriosis Current Management and Future Trends. India: Jaypee Brpthers Medical Publishers Ltd; 2009:226.
9. OB Ioffe RJ Zaino GL Mutter 2009 Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator Mod Pathol 22 3 450 459 19136935 10.1038/modpathol.2008.204 1:CAS:528:DC%2BD1MXisVSnt74%3D
10. GR Jang SA Wrighton LZ Benet 1996 Identification of CYP3A4 as the principal enzyme catalyzing mifepristone (RU 486) oxidation in human liver microsomes Biochem Pharmacol 52 5 753 761 8765473 10.1016/0006-2952(96)00357-7 1:CAS:528:DyaK28XltFOrsLs%3D (Pubitemid 26276491)
11. KK Khan YQ He MA Correia JR Halpert 2002 Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4 Drug Metab Dispos 30 9 985 990 12167563 10.1124/dmd.30.9.985 1:CAS:528:DC%2BD38XmsVShurs%3D
12. Beal S, Sheiner LB, Boeckmann A, Bauer RJ. NONMEM User's Guide. Elliot City: ICON Development Solutions; 2009.
13. EN Jonsson MO Karlsson 1999 Xpose-an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM Comput Methods Programs Biomed 58 1 51 64 10195646 10.1016/S0169-2607(98)00067-4 1:STN:280:DyaK1M3htVShsw%3D%3D (Pubitemid 29049052)
14. EN Jonsson MO Karlsson 1998 Automated covariate model building within NONMEM Pharm Res 15 9 1463 1468 9755901 10.1023/A:1011970125687 1:CAS:528:DyaK1cXmtFyhu7o%3D (Pubitemid 28427937)
15. KC Carlsson RM Savic AC Hooker MO Karlsson 2009 Modeling subpopulations with the $MIXTURE subroutine in NONMEM: finding the individual probability of belonging to a subpopulation for the use in model analysis and improved decision making AAPS J 11 1 148 154 19277871 10.1208/s12248-009-9093-4
16. L Lindbom J Ribbing EN Jonsson 2004 Perl-speaks-NONMEM (PsN)-a Perl module for NONMEM-related programming Comput Methods Programs Biomed 75 2 85 94 15212851 10.1016/j.cmpb.2003.11.003 (Pubitemid 38798039)
17. AD Huitema RA Mathot MM Tibben JH Schellens S Rodenhuis JH Beijnen 2001 Population pharmacokinetics of thioTEPA and its active metabolite TEPA in patients undergoing high-dose chemotherapy Br J Clin Pharmacol. 51 1 61 70 11167666 10.1046/j.1365-2125.2001.01301.x 1:CAS:528:DC%2BD3MXhtF2hu7Y%3D (Pubitemid 32118821)
18. JN Barnes AJ Williams MJ Tomson PA Toseland FJ Goodwin 1985 Dihydrocodeine in renal failure: further evidence for an important role of the kidney in the handling of opioid drugs Br Med J (Clin Res Ed) 290 6470 740 742 10.1136/bmj.290.6470.740 1:STN:280:DyaL2M7itlKqtw%3D%3D (Pubitemid 15103836)
19. PT McNamee GW Moore MG McGeown CC Doherty BJ Collins 1985 Gastric emptying in chronic renal failure Br Med J (Clin Res Ed) 291 6491 310 311 10.1136/bmj.291.6491.310 1:STN:280:DyaL2M3ltlygsA%3D%3D (Pubitemid 15045112)
20. MA Perazella C Parikh 2005 Pharmacology Am J Kidney Dis 46 6 1129 1139 16310580 10.1053/j.ajkd.2005.07.051
21. D Brown-Cartwright HJ Smith M Feldman 1988 Gastric emptying of an indigestible solid in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis Gastroenterology 95 1 49 51 3371624 1:STN:280:DyaL1c3isF2gsw%3D%3D
22. YW Lam S Banerji C Hatfield RL Talbert 1997 Principles of drug administration in renal insufficiency Clin Pharmacokinet 32 1 30 57 9012555 10.2165/00003088-199732010-00002 1:CAS:528:DyaK2sXhtVWjsr0%3D (Pubitemid 27037847)
23. TD Nolin RF Frye GR Matzke 2003 Hepatic drug metabolism and transport in patients with kidney disease Am J Kidney Dis 42 5 906 925 14582035 10.1016/j.ajkd.2003.07.019 1:CAS:528:DC%2BD3sXpt1Ogtbk%3D (Pubitemid 37322908)
24. S Gabardi S Abramson 2005 Drug dosing in chronic kidney disease Med Clin North Am 89 3 649 687 15755472 10.1016/j.mcna.2004.11.007 1:CAS:528: DC%2BD2MXjsV2mtr0%3D (Pubitemid 40332402)
25. F Sata A Sapone G Elizondo, et al. 2000 CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity Clin Pharmacol Ther 67 1 48 56 10668853 10.1067/mcp.2000.104391 1:CAS:528:DC%2BD3cXhtV2rtrw%3D (Pubitemid 30078387)
26. JK Lamba YS Lin EG Schuetz KE Thummel 2002 Genetic contribution to variable human CYP3A-mediated metabolism Adv Drug Deliv Rev 54 10 1271 1294 12406645 10.1016/S0169-409X(02)00066-2 1:CAS:528:DC%2BD38XotF2jurY%3D (Pubitemid 35284253)
27. SA Wrighton WR Brian MA Sari, et al. 1990 Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3) Mol Pharmacol 38 2 207 213 2385232 1:CAS:528:DyaK3cXlt12ku78%3D (Pubitemid 20255306)
28. MF Paine M Khalighi JM Fisher, et al. 1997 Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism J Pharmacol Exp Ther 283 3 1552 1562 9400033 1:CAS:528: DyaK1cXis1yquw%3D%3D (Pubitemid 28016533)
29. JC Gorski SD Hall DR Jones M VandenBranden SA Wrighton 1994 Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily Biochem Pharmacol 47 9 1643 1653 8185679 10.1016/0006-2952(94)90543-6 1:CAS:528:DyaK2cXksV2mtLg%3D (Pubitemid 24167278)
30. E Hustert M Haberl O Burk, et al. 2001 The genetic determinants of the CYP3A5 polymorphism Pharmacogenetics 11 9 773 779 11740341 10.1097/00008571- 200112000-00005 1:CAS:528:DC%2BD38XnsFKqsrk%3D (Pubitemid 33151512)