Núria Buil-Bruna1, María Jesús Garrido1, Marion Dehez2, Amandine Manon2, Thi Xuan Quyen Nguyen2, Edda L Gomez-Panzani2, Iñaki F Trocóniz3,4. 1. Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Irunlarrea 1, 31080, Pamplona, Spain. 2. Clinical Pharmacokinetics, Pharmacokinetics and Drug Metabolism, Ipsen Innovation, Les Ulis, France. 3. Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Irunlarrea 1, 31080, Pamplona, Spain. itroconiz@unav.es. 4. IdisNA, Navarra Institute for Health Research, Pamplona, Spain. itroconiz@unav.es.
Abstract
BACKGROUND AND OBJECTIVES: Lanreotide Autogel (lanreotide Depot in the USA) has demonstrated anti-tumor activity and control of the symptoms associated with hormone hypersecretion in patients with neuroendocrine tumors. The objectives of this study were to describe the pharmacokinetics of lanreotide Autogel administered 4-weekly by deep subcutaneous injections of 60, 90, or 120 mg in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), to quantify the magnitude of inter-patient variability (IPV), and to identify those patient characteristics that impact on pharmacokinetics. METHODS: Analyses were based on pooled data from clinical trials. A total of 1541 serum concentrations from 290 patients were analyzed simultaneously by the population approach using NONMEM version 7.2. Covariates evaluated included demographics, renal and hepatic function markers, and disease-related parameters. RESULTS: Serum profiles were described by a one-compartment disposition model in which the absorption process was characterized by two parallel pathways following first- and zero-order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day, representing a substantial difference in clearance in this population of patients with respect to healthy volunteers that could not be explained by any of the covariates tested. Body weight was the only covariate to show a statistically significant effect on the pharmacokinetic profile, but due to the overlap between the pharmacokinetic profiles of patients with lower or higher body weights the effect of body weight on clearance was not considered clinically relevant. The IPV was low for clearance (27%) and moderate to high for volume of distribution (150%) and the absorption constant (61%). CONCLUSIONS: Using two mechanisms of absorption, the pharmacokinetics of lanreotide Autogel were well-described in patients with GEP-NET. None of the patient characteristics tested were of clinical relevance to potential dose adjustment in clinical practice.
BACKGROUND AND OBJECTIVES: Lanreotide Autogel (lanreotide Depot in the USA) has demonstrated anti-tumor activity and control of the symptoms associated with hormone hypersecretion in patients with neuroendocrine tumors. The objectives of this study were to describe the pharmacokinetics of lanreotide Autogel administered 4-weekly by deep subcutaneous injections of 60, 90, or 120 mg in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), to quantify the magnitude of inter-patient variability (IPV), and to identify those patient characteristics that impact on pharmacokinetics. METHODS: Analyses were based on pooled data from clinical trials. A total of 1541 serum concentrations from 290 patients were analyzed simultaneously by the population approach using NONMEM version 7.2. Covariates evaluated included demographics, renal and hepatic function markers, and disease-related parameters. RESULTS: Serum profiles were described by a one-compartment disposition model in which the absorption process was characterized by two parallel pathways following first- and zero-order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day, representing a substantial difference in clearance in this population of patients with respect to healthy volunteers that could not be explained by any of the covariates tested. Body weight was the only covariate to show a statistically significant effect on the pharmacokinetic profile, but due to the overlap between the pharmacokinetic profiles of patients with lower or higher body weights the effect of body weight on clearance was not considered clinically relevant. The IPV was low for clearance (27%) and moderate to high for volume of distribution (150%) and the absorption constant (61%). CONCLUSIONS: Using two mechanisms of absorption, the pharmacokinetics of lanreotide Autogel were well-described in patients with GEP-NET. None of the patient characteristics tested were of clinical relevance to potential dose adjustment in clinical practice.
Authors: Christoffer W Tornøe; Henrik Agersø; Thomas Senderovitz; Henrik A Nielsen; Henrik Madsen; Mats O Karlsson; E Niclas Jonsson Journal: Br J Clin Pharmacol Date: 2006-11-10 Impact factor: 4.335
Authors: Martyn E Caplin; Marianne Pavel; Jarosław B Ćwikła; Alexandria T Phan; Markus Raderer; Eva Sedláčková; Guillaume Cadiot; Edward M Wolin; Jaume Capdevila; Lucy Wall; Guido Rindi; Alison Langley; Séverine Martinez; Joëlle Blumberg; Philippe Ruszniewski Journal: N Engl J Med Date: 2014-07-17 Impact factor: 91.245
Authors: Marta Martín-Richard; Bartomeu Massutí; Eva Pineda; Vicente Alonso; Maribel Marmol; Daniel Castellano; Emilio Fonseca; Antonio Galán; Marta Llanos; Maria Angeles Sala; Carlos Pericay; Fernando Rivera; Javier Sastre; Angel Segura; Maria Quindós; Pascal Maisonobe Journal: BMC Cancer Date: 2013-09-20 Impact factor: 4.430
Authors: Florian Bösch; Alexandr V Bazhin; Sabine Heublein; Katharina Brüwer; Thomas Knösel; Florian P Reiter; Christoph J Auernhammer; Markus O Guba; Christine Spitzweg; Jens Werner; Martin K Angele Journal: BMC Cancer Date: 2019-06-13 Impact factor: 4.430