Pharmacodynamic Modeling of the Effects of Lanreotide Autogel on Growth Hormone and Insulin‐Like Growth Factor 1
- 1 April 2012
- journal article
- research article
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 52 (4), 487-498
- https://doi.org/10.1177/0091270011399761
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.Keywords
This publication has 26 references indexed in Scilit:
- Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel® therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extensionPituitary, 2009
- Significant tumour shrinkage after 12 months of lanreotide Autogel‐120 mg treatment given first‐line in acromegalyClinical Endocrinology, 2009
- Population Pharmacokinetic Analysis of Lanreotide Autogel® in Healthy SubjectsClinical Pharmacokinetics, 2009
- Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48weeks in patients with acromegalyClinical Endocrinology, 2008
- Home administration of lanreotide Autogel® by patients with acromegaly, or their partners, is safe and effectiveClinical Endocrinology, 2007
- Efficacy of a slow‐release formulation of lanreotide (Autogel® 120 mg) in patients with acromegaly previously treated with octreotide long acting release (LAR): an open, multicentre longitudinal studyClinical Endocrinology, 2007
- Efficacy of lanreotide Autogel® administered every 4–8 weeks in patients with acromegaly previously responsive to lanreotide microparticles 30 mg: a phase III trialClinical Endocrinology, 2006
- Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegalyActa Endocrinologica, 2006
- Population PK and PK/PD modelling of microencapsulated octreotide acetate in healthy subjectsBritish Journal of Clinical Pharmacology, 2000
- Comparison of four basic models of indirect pharmacodynamic responsesJournal of Pharmacokinetics and Biopharmaceutics, 1993