Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months

BACKGROUND AND OBJECTIVE: Lanreotide is a somatostatin analogue used for the treatment of acromegaly and neuroendocrine tumours. The objective of this study was to develop a pharmacokinetic model for the sustained-release formulation lanreotide Autogel after deep subcutaneous administration in healt...

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Autores: Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44, Cendros, J.M. (Josep Maria)|||/items/2ae5e429-96ea-49c1-88e8-f56d5b2a499a, Peraire, C. (Concepción)|||/items/4b20a69b-9272-44dd-954a-cb446dd8784b, Ramis, J. (Joaquim)|||/items/dac6919a-34d8-4e3e-899b-485caa838888, Garrido-Cid, M.J. (María Jesús)|||/items/02b0ddd8-23bb-4f81-8a99-5d1296b3c703, Boscani, P. (Paolo)|||/items/ac3ff526-2374-4d95-8737-b52de3895b43, Obach, R. (Rosendo)|||/items/29e9a3a2-3c00-4d13-8e1c-dcf72fdae23c
Tipo de recurso: artículo
Fecha de publicación:2009
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/21759
Acceso en línea:https://hdl.handle.net/10171/21759
Access Level:acceso abierto
Palabra clave:Lanreotide Autogel pharmacokinetics
Neuroendocrine tumours
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oai_identifier_str oai:dadun.unav.edu:10171/21759
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
title Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
spellingShingle Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
Lanreotide Autogel pharmacokinetics
Neuroendocrine tumours
title_short Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
title_full Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
title_fullStr Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
title_full_unstemmed Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
title_sort Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 months
dc.creator.none.fl_str_mv Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
Cendros, J.M. (Josep Maria)|||/items/2ae5e429-96ea-49c1-88e8-f56d5b2a499a
Peraire, C. (Concepción)|||/items/4b20a69b-9272-44dd-954a-cb446dd8784b
Ramis, J. (Joaquim)|||/items/dac6919a-34d8-4e3e-899b-485caa838888
Garrido-Cid, M.J. (María Jesús)|||/items/02b0ddd8-23bb-4f81-8a99-5d1296b3c703
Boscani, P. (Paolo)|||/items/ac3ff526-2374-4d95-8737-b52de3895b43
Obach, R. (Rosendo)|||/items/29e9a3a2-3c00-4d13-8e1c-dcf72fdae23c
author Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
author_facet Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
Cendros, J.M. (Josep Maria)|||/items/2ae5e429-96ea-49c1-88e8-f56d5b2a499a
Peraire, C. (Concepción)|||/items/4b20a69b-9272-44dd-954a-cb446dd8784b
Ramis, J. (Joaquim)|||/items/dac6919a-34d8-4e3e-899b-485caa838888
Garrido-Cid, M.J. (María Jesús)|||/items/02b0ddd8-23bb-4f81-8a99-5d1296b3c703
Boscani, P. (Paolo)|||/items/ac3ff526-2374-4d95-8737-b52de3895b43
Obach, R. (Rosendo)|||/items/29e9a3a2-3c00-4d13-8e1c-dcf72fdae23c
author_role author
author2 Cendros, J.M. (Josep Maria)|||/items/2ae5e429-96ea-49c1-88e8-f56d5b2a499a
Peraire, C. (Concepción)|||/items/4b20a69b-9272-44dd-954a-cb446dd8784b
Ramis, J. (Joaquim)|||/items/dac6919a-34d8-4e3e-899b-485caa838888
Garrido-Cid, M.J. (María Jesús)|||/items/02b0ddd8-23bb-4f81-8a99-5d1296b3c703
Boscani, P. (Paolo)|||/items/ac3ff526-2374-4d95-8737-b52de3895b43
Obach, R. (Rosendo)|||/items/29e9a3a2-3c00-4d13-8e1c-dcf72fdae23c
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Lanreotide Autogel pharmacokinetics
Neuroendocrine tumours
topic Lanreotide Autogel pharmacokinetics
Neuroendocrine tumours
description BACKGROUND AND OBJECTIVE: Lanreotide is a somatostatin analogue used for the treatment of acromegaly and neuroendocrine tumours. The objective of this study was to develop a pharmacokinetic model for the sustained-release formulation lanreotide Autogel after deep subcutaneous administration in healthy subjects, and to explore the potential effect of covariates, especially sex and dose. SUBJECTS AND METHODS: This was an open-label, single-centre, randomized, dose-ranging, parallel-group study, with a follow-up period of 4-7 months following drug administration in healthy subjects. Healthy Caucasian subjects aged 18-45 years were included. Subjects received a rapid intravenous bolus of 7 microg/kg of an immediate-release formulation of lanreotide (lanreotide IRF). After a 3-day washout period, participants were randomized to receive a single deep subcutaneous injection of lanreotide Autogel at a dose of 60, 90 or 120 mg. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Blood samples for lanreotide determination were obtained during the first 12 hours after the intravenous bolus injection and during the 4- to 7-month follow-up period after deep subcutaneous administration of lanreotide Autogel. Data after intravenous and subcutaneous administration were fitted simultaneously using the population approach in NONMEM((R)) version VI software. The model was validated externally using data from patients with acromegaly. RESULTS: In total, 50 healthy subjects (24 women and 26 men) received a single intravenous dose of lanreotide IRF. Of these, 38 subjects (18 women and 20 men) received a single subcutaneous dose of lanreotide Autogel 3 days after intravenous lanreotide IRF. The disposition of lanreotide was described by a three-compartment open model. The estimates of the total volume of distribution and serum clearance were 15.1 L and 23.1 L/h, respectively. The estimates of interindividual variability were <40%. To evaluate lanreotide Autogel pharmacokinetics, the absorption rate was modelled to decrease exponentially as a function of the natural logarithm of time. The absolute bioavailability after deep subcutaneous administration of lanreotide Autogel was 63%. The rate of absorption and bioavailability of lanreotide Autogel were independent of the administered dose in the range from 60 to 120 mg, and no significant effect of covariates (sex, dose, age or bodyweight) was found (p > 0.05). CONCLUSIONS: Population analysis allows a full description of the disposition of lanreotide after rapid intravenous bolus administration of lanreotide IRF (7 microg/kg) and the pharmacokinetics of lanreotide Autogel after a single deep subcutaneous injection (60, 90 or 120 mg) in healthy subjects. The model-based simulations provide support for the feasibility of extending the dosing interval for lanreotide Autogel to 56 days when given at 120 mg. The absorption profile of lanreotide Autogel was independent of the dose and was not affected by sex.
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-01-01
2009
2009-01-01
2012
2012-04-24
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/21759
url https://hdl.handle.net/10171/21759
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Adis Press
publisher.none.fl_str_mv Adis Press
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy Subjects: evidence for injection interval of up to 2 monthsTroconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44Cendros, J.M. (Josep Maria)|||/items/2ae5e429-96ea-49c1-88e8-f56d5b2a499aPeraire, C. (Concepción)|||/items/4b20a69b-9272-44dd-954a-cb446dd8784bRamis, J. (Joaquim)|||/items/dac6919a-34d8-4e3e-899b-485caa838888Garrido-Cid, M.J. (María Jesús)|||/items/02b0ddd8-23bb-4f81-8a99-5d1296b3c703Boscani, P. (Paolo)|||/items/ac3ff526-2374-4d95-8737-b52de3895b43Obach, R. (Rosendo)|||/items/29e9a3a2-3c00-4d13-8e1c-dcf72fdae23cLanreotide Autogel pharmacokineticsNeuroendocrine tumoursBACKGROUND AND OBJECTIVE: Lanreotide is a somatostatin analogue used for the treatment of acromegaly and neuroendocrine tumours. The objective of this study was to develop a pharmacokinetic model for the sustained-release formulation lanreotide Autogel after deep subcutaneous administration in healthy subjects, and to explore the potential effect of covariates, especially sex and dose. SUBJECTS AND METHODS: This was an open-label, single-centre, randomized, dose-ranging, parallel-group study, with a follow-up period of 4-7 months following drug administration in healthy subjects. Healthy Caucasian subjects aged 18-45 years were included. Subjects received a rapid intravenous bolus of 7 microg/kg of an immediate-release formulation of lanreotide (lanreotide IRF). After a 3-day washout period, participants were randomized to receive a single deep subcutaneous injection of lanreotide Autogel at a dose of 60, 90 or 120 mg. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Blood samples for lanreotide determination were obtained during the first 12 hours after the intravenous bolus injection and during the 4- to 7-month follow-up period after deep subcutaneous administration of lanreotide Autogel. Data after intravenous and subcutaneous administration were fitted simultaneously using the population approach in NONMEM((R)) version VI software. The model was validated externally using data from patients with acromegaly. RESULTS: In total, 50 healthy subjects (24 women and 26 men) received a single intravenous dose of lanreotide IRF. Of these, 38 subjects (18 women and 20 men) received a single subcutaneous dose of lanreotide Autogel 3 days after intravenous lanreotide IRF. The disposition of lanreotide was described by a three-compartment open model. The estimates of the total volume of distribution and serum clearance were 15.1 L and 23.1 L/h, respectively. The estimates of interindividual variability were <40%. To evaluate lanreotide Autogel pharmacokinetics, the absorption rate was modelled to decrease exponentially as a function of the natural logarithm of time. The absolute bioavailability after deep subcutaneous administration of lanreotide Autogel was 63%. The rate of absorption and bioavailability of lanreotide Autogel were independent of the administered dose in the range from 60 to 120 mg, and no significant effect of covariates (sex, dose, age or bodyweight) was found (p > 0.05). CONCLUSIONS: Population analysis allows a full description of the disposition of lanreotide after rapid intravenous bolus administration of lanreotide IRF (7 microg/kg) and the pharmacokinetics of lanreotide Autogel after a single deep subcutaneous injection (60, 90 or 120 mg) in healthy subjects. The model-based simulations provide support for the feasibility of extending the dosing interval for lanreotide Autogel to 56 days when given at 120 mg. The absorption profile of lanreotide Autogel was independent of the dose and was not affected by sex.Adis PressDadun. Depósito Académico Digital Universidad de Navarra20122012-04-2420092009-01-0120092009-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21759reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/217592026-06-21T12:47:57Z
score 15,300719

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