Assessment of the absorption, metabolism and excretion of [ 14C]pasireotide in healthy volunteers using accelerator mass spectrometry

Cancer Chemotherapy and Pharmacology

Volumn 72, Issue 1, 2013, Pages 181-188

  Lin, T H ^a   Hu, K ^a   Flarakos, J ^a   Sharr Mcmahon, M ^a   Mangold, J B ^a   He, H ^a   Wang, Y ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Absorption, distribution, metabolism and excretion (ADME); Accelerator mass spectrometry (AMS); Healthy volunteers; Pasireotide; Pharmacokinetics

Indexed keywords

CARBON PASIREOTIDE C 14; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BACKACHE; BLOOD SAMPLING; CLINICAL TRIAL; DIZZINESS; DOSE RESPONSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG FATALITY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG URINE LEVEL; EPISTAXIS; FECES ANALYSIS; FLATULENCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; INJECTION SITE REACTION; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MORNING DOSAGE; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RADIOIMMUNOASSAY; STOMACH DISCOMFORT; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADOLESCENT; ADULT; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; BIOTRANSFORMATION; CARBON RADIOISOTOPES; FECES; HALF-LIFE; HUMANS; INJECTIONS, SUBCUTANEOUS; INTESTINAL ABSORPTION; MALE; METABOLIC CLEARANCE RATE; PLASMA; RECEPTORS, SOMATOSTATIN; SOMATOSTATIN; URINE; YOUNG ADULT;

EID: 84879793521     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-013-2183-0     Document Type: Article

References (15)

1. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146:707-716
2. Petersenn S, Schopohl J, Barkan A, Mohideen P, Colao A, Abs R, Buchelt A, Ho Y-Y, Hu K, Farrall AJ, Melmed S, Biller BM (2010) Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, Phase II trial. J Clin Endocrinol Metab 95:2781-2789
3. Colao A, Bronstein M, Freda P, Gu F, Shen C-C, Gadelha M, Fleseriu M, Hermosillo Resendiz K, Ruffin M, Chen Y, Sheppard MC (2012) Pasireotide LAR is significantly more effective than octreotide LAR at inducing biochemical control in patients with acromegaly: results of a 12-month randomized, double-blind, multicenter, Phase III study. Endocrine Abstr 29:abst OC1.1
4. Kvols L, Glusman JE, Hahn EA, Wang E, Öberg K, Anthony L, O'Dorisio TM, de Herder W, Darby CH, Wiedenmann B, The Pasireotide Carcinoid Study Group (2007) The effects of pasireotide (SOM230) on health-related quality of life in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR. J Clin Oncol 25(18S):abst 4558
5. Novartis Pharma AG. Signifor Summary of Product Characteristics (2012) Available at: http://www.signifor.com/european-product-characteristics.jsp (last Accessed Feb 2013)
6. Petersenn S, Hu K, Maldonado M, Zhang Y, Lasher J, Bouillaud E, Wang Y, Mann K, Unger N (2012) Tolerability and dose-proportional pharmacokinetics of pasireotide administered as a single dose or two divided doses in healthy male volunteers: a single-center, open-label, ascending-dose study. Clin Ther 34:677-688
7. Petersenn S, Unger N, Hu K, Weisshaar B, Zhang Y, Bouillaud E, Hermosillo Resendiz K, Wang Y, Mann K (2012) Pasireotide (SOM230), a novel multi-receptor-targeted somatostatin analogue, is well tolerated when administered as a continuous 7-day subcutaneous infusion in healthy male volunteers. J Clin Pharmacol 52:1017-1027
8. Ma P, Wang Y, Van Der Hoek J, Nedelman J, Schran H, Tran L-L, Lamberts SW (2005) Pharmacokinetic-pharmacodynamic comparison of a novel multiligand somatostatin analog, SOM230, with octreotide in patients with acromegaly. Clin Pharmacol Ther 78:69-80
9. Golor G, Hu K, Ruffin M, Buchelt A, Bouillaud E, Wang Y, Maldonado M (2012) A first-in-man study to evaluate the safety, tolerability and pharmacokinetics of pasireotide (SOM230), a multireceptor-targeted somatostatin analog, in healthy volunteers. Drug Des Devel Ther 6:71-79
10. Horsmans Y, Hu K, Ruffin M, Wang Y, Song D, Bouillaud E, Wang Y, Mazur D, Botha FP, Heuman DM (2012) Effect of hepatic impairment on the pharmacokinetics of pasireotide (SOM230): results from a multicenter Phase I study. J Clin Pharmacol 52:552-558
11. Bazett HC (1920) An analysis of the time-relations of electrocardiograms. Heart 7:353-370
12. Arjomand A (2010) Accelerator mass spectrometry-enabled studies: current status and future prospects. Bioanalysis 2:519-541
13. Hamilton RA, Garnett WR, Kline BJ (1981) Determination of mean valproic acid serum level by assay of a single pooled sample. Clin Pharmacol Ther 29:408-413
14. Roffey SJ, Obach RS, Gedge JI, Smith DA (2007) What is the objective of the mass balance study? A retrospective analysis of data in animal and human excretion studies employing radiolabeled drugs. Drug Metab Rev 39:17-43
15. Beglinger C, Hu K, Wang Y, Bouillaud E, Darstein C, Wang Y, Mohideen P (2012) Multiple once-daily subcutaneous doses of pasireotide were well tolerated in healthy male volunteers: a randomized, double-blind, placebo-controlled, cross-over, Phase I study. Endocrine 42:366-374