title: Pharmacodynamic modeling of the effects of lanreotide Autogel on growth hormone and insulin-like growth factor 1.
abstract: Acromegaly arises from excessive levels of growth hormone (GH), many of whose effects are mediated by stimulation of secretion of insulin-like growth factor 1 (IGF-1). Synthetic somatostatin analogues inhibit GH secretion. The objective of the study was to develop a population pharmacodynamic model describing the relationship between serum concentrations of lanreotide (C(P)) and its GH and IGF-1 effects in patients with acromegaly receiving lanreotide Autogel (LA) at doses of 60, 90, or 120 mg by deep subcutaneous route every 28 days. Data were analyzed from 104 patients. The GH and IGF-1 profiles were fit simultaneously using the population approach with NONMEM. The GH vs C(P) and the IGF-1 vs GH relationships were described using inhibitory I(max) and E(max) models, respectively. Results indicated that lanreotide cannot abolish GH completely. C(P) levels of 3.4 ng/mL are required to achieve percentages of hormonal control (GH and IGF-1) of 21% and 36% in not treated and previously treated patients. If the focus is only GH, a C(P) of 3.4 ng/mL corresponds to 33% and 56% controlling rates. Simulations showed that there is a possible clinical benefit if the highest dose of 120 mg LA is administered to patients who are not well controlled by lower doses of LA.
authors.affiliation: Pharmacy and Pharmaceutical Technology, School of Pharmacy,University of Navarra, Pamplona, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Garrido
authors.forename: Josep-María
authors.initials: JM
authors.lastname: Cendrós
authors.forename: Joaquim
authors.initials: J
authors.lastname: Ramis
authors.forename: Concepción
authors.initials: C
authors.lastname: Peraire
authors.forename: Rosendo
authors.initials: R
authors.lastname: Obach
authors.forename: Iñaki F
authors.initials: IF
authors.lastname: Trocóniz
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D005782:Gels; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016037:Single-Blind Method; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone