Long-acting octreotide and prolonged-release lanreotide formulations have different pharmacokinetic profiles

被引:96
作者
Astruc, B
Marbach, P
Bouterfa, H
Denot, C
Safari, M
Vitaliti, A
Sheppard, M
机构
[1] Novartis Pharma AG, Drug Metab & Pharmacokinet, CH-4002 Basel, Switzerland
[2] Univ Birmingham, Birmingham B15 2TT, W Midlands, England
关键词
long-acting octreotide; prolonged-release lanreotide; safety/tolerability; pharmacokinetics; modeling;
D O I
10.1177/0091270005277936
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Single-dose pharmacokinetic (PK) profiles and multiple-dose PK modeling were compared for long-acting octreotide (20 or 60 mg) and prolonged-release lanreotide (90 or 120 mg) over 91 days; steady-state profiles were simulated. All treatments were well tolerated. Octreotide 20-mg profile showed increased concentration on clay 1, lag from days 2 to 6, then prolonged plateau phase (days 11-41); 60-mg PK was dose proportionol. Lonreotide 90-mg profile showed C-max on day 1 then elimination (apparent t(1/2) 25.5 days); 120-mg profile was underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a C-mean of 1216 pg/mL (range, 1065-1585) with low fluctuation index (43%). Steady-state PK of lanreotide 90 mgl 28 d suggested a C-mean of 4455 pglmL (range, 2499-9279) with high fluctuation index (152%). Long-acting octreotide had more predictable PK than prolonged-release lanreotide. Simulated steady-state profiles suggest long-acting octreotide could be optimized to meet individual patient needs. In contrast, proloned-release lanreotide requires exposure canstantly above the therapeutic target to enable monthly long-term therapy.
引用
收藏
页码:836 / 844
页数:9
相关论文
共 42 条
  • [1] Pharmacokinetics of a new autogel formulation of the somatostatin analogue lanreotide after a single subcutaneous dose in healthy volunteers
    Antonijoan, RM
    Barbanoj, MJ
    Cordero, JA
    Peraire, C
    Obach, R
    Vallès, J
    Chérif-Cheikh, R
    Torres, M
    Bismuth, F
    Montes, M
    [J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 2004, 56 (04) : 471 - 476
  • [2] The efficacy and safety of lanreotide Autogel in patients with acromegaly previously treated with octreotide LAR
    Ashwell, SG
    Bevan, JS
    Edwards, OM
    Harris, MM
    Holmes, C
    Middleton, MA
    James, RA
    [J]. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2004, 150 (04) : 473 - 480
  • [3] SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile
    Bruns, C
    Lewis, I
    Briner, U
    Meno-Tetang, G
    Weckbecker, G
    [J]. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2002, 146 (05) : 707 - 716
  • [4] MOLECULAR PHARMACOLOGY OF SOMATOSTATIN-RECEPTOR SUBTYPES
    BRUNS, C
    WECKBECKER, G
    RAULF, F
    KAUPMANN, K
    SCHOEFFTER, P
    HOYER, D
    LUBBERT, H
    [J]. MOLECULAR AND CELL BIOLOGICAL ASPECTS OF GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR DISEASE, 1994, 733 : 138 - 146
  • [5] One-year follow-up of patients with acromegaly treated with fixed or titrated doses of lanreotide Autogel®
    Caron, P
    Bex, M
    Cullen, DR
    Feldt-Rasmussen, U
    Pico Alfonso, AM
    Pynka, S
    Racz, K
    Schopohl, J
    Tabarin, A
    Valimaki, MJ
    [J]. CLINICAL ENDOCRINOLOGY, 2004, 60 (06) : 734 - 740
  • [6] Caron P, 2002, ANN ENDOCRINOL-PARIS, V63, pS19
  • [7] Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly
    Caron, P
    Beckers, A
    Cullen, DR
    Goth, MI
    Gutt, B
    Laurberg, P
    Pico, AM
    Valimaki, M
    Zgliczynski, W
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (01) : 99 - 104
  • [8] CENDROS JM, 2003, END ABSTR P47, V6
  • [9] Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly
    Chanson, P
    Boerlin, V
    Ajzenberg, C
    Bachelot, Y
    Benito, P
    Bringer, J
    Caron, P
    Charbonnel, B
    Cortet, C
    Delemer, B
    Escobar-Jiménez, F
    Foubert, L
    Gaztambide, S
    Jockenhoevel, F
    Kuhn, JM
    Leclere, J
    Lorcy, Y
    Perlemuter, L
    Prestele, H
    Roger, P
    Rohmer, V
    Santen, R
    Sassolas, G
    Scherbaum, WA
    Schopohl, J
    Torres, E
    Varela, C
    Villamil, F
    Webb, SM
    [J]. CLINICAL ENDOCRINOLOGY, 2000, 53 (05) : 577 - 586
  • [10] CLINICAL PHARMACOKINETICS OF OCTREOTIDE - THERAPEUTIC APPLICATIONS IN PATIENTS WITH PITUITARY-TUMORS
    CHANSON, P
    TIMSIT, J
    HARRIS, AG
    [J]. CLINICAL PHARMACOKINETICS, 1993, 25 (05) : 375 - 391