Pharmacokinetic study and effects on growth hormone secretion in healthy volunteers of the new somatostatin analogue BIM 23014

Kuhn, Jean-Marc; Basin, C; Mollard, M.; Rouge, Baton; Baudoin, Christian; Obach, R.; Tolis, G.

doi:10.1007/bf00315353

Cited by 23 publications

(13 citation statements)

References 28 publications

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“…The somatostatin analogue is encapsulated in a polyactide-polyglycolide copolymer. Previous studies showed that the daily lanreotide dose required to reduce plasma GH levels ranges from 1000 to 2000 mg day-' [26] in acromegalic patients.…”

Section: Productmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic properties of a long‐acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.

Kuhn

Legrand

Ruiz

et al. 1994

Brit J Clinical Pharma

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1 The aims of the study were to assess the pharmacokinetic parameters and the hormonal effects of the slow-release formulation of the somatostatin analogue (SR-L) in normal male volunteers. 2 Eight healthy males were studied. For the determination of basal values blood was sampled before the injection of vehicle and then every other hour for 8 h in order to measure plasma GH, prolactin (PRL), TSH, free thyroxin (fT4), insulin and glucagon levels. Plasma insulin-like growth factor 1 (IGF-1) levels were measured on a single sample. On day 1 of the study, 30 mg SR-L was administered intramuscularly. Blood was drawn just before injection and then every other hour for a period of 8 h. Thereafter, blood was sampled three times a week for 3 weeks in order to measure lanreotide, IGF-1, TSH, ff4 and PRL concentrations. Plasma GH was determined on days 6 and 11 of the study.3 Plasma lanreotide concentrations rose to 38.3 ± 4.1 ng ml-' 2 h following injection. The levels then progressively decreased, remaining above 1.5 ng ml-' until day 11 and reaching 0.92 ± 0.28 ng ml-' 2 weeks after injection. The apparent plasma half-life and mean residence time were 4.52 ± 0.50 and 5.48 ± 0.51 days respectively. 4 By comparison with the control day, plasma insulin concentrations only decreased 2 h following injection, whereas plasma glucagon did not change at any time. 5 Plasma TSH concentrations were significantly (P < 0.01) reduced from 2 h to day 4 following SR-L injection. ff4 concentrations dropped significantly (P < 0.01) from day 2 to day 4 but always remained within the normal adult range.6 Plasma GH concentrations were constantly below 0.2 ng ml-' whereas plasma IGF-l concentrations were significantly (P < 0.05) reduced from day 4 to day 14 following SR-L injection. No significant changes in plasma PRL levels were observed. 7 These results show that lanreotide administered in slow-release formulation to normal healthy males decreases transiently plasma insulin and TSH, and consecutively fT4 levels, without affecting either PRL or glucagon secretion. In contrast, SR-L reduces IGF-I levels (likely through a decrease in GH secretion) for at least 14 days. This indicates that SR-L could be injected every 14 days to decrease IGF-1 levels. 8 This slow-release formulation may be very convenient for the treatment of diseases for which a lowering of IGF-1 levels is essential, without side effects on glucose homeostasis and thyroid function.

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Section: Productmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic properties of a long‐acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.

Kuhn

Legrand

Ruiz

et al. 1994

Brit J Clinical Pharma

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“…The synthetic somatostatin analogues, lanreotide and octreotide, have longer plasma half-lives of 90 and 110 min respectively (8,9). However, multiple daily injections or continuous subcutaneous infusion of these drugs remains a necessity and this detracts from patient acceptability.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of lanreotide Autogel in patients with acromegaly previously treated with octreotide LAR

Ashwell

Bevan

Edwards

et al. 2004

European Journal of Endocrinology

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Objective: Lanreotide Autogel is a sustained-release aqueous gel formulation supplied in a prefilled syringe, with injection volume , 0.5 ml. The aim of this study was to establish the efficacy and safety of Autogel in patients with acromegaly previously treated with octreotide LAR. Design: A 28-week, open, multicentre study. Patients: Twelve patients with acromegaly, treated with 20 mg octreotide LAR for . 4 months, with serum GH levels , 10.0 mU/l. Methods: Autogel (90 mg) was given every 28 days during weeks 0-12. At week 16 the dose was titrated based on GH levels at weeks 8 and 12. If GH levels were ,2.0, 2.0-5.0, or . 5.0 mU/l, Autogel was reduced to 60 mg, maintained at 90 mg, or increased to 120 mg respectively, for the next three injections. GH and IGF-I levels were reassessed at weeks 24 and 28.

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“…The disposition half‐life ranges from 80 to 100 min for both routes of administration, which is more than 30 times that of sst. A similar favorable pharmakokinetic is observed with lanreotide 88. These sst analogs can therefore be administered to patients by subcutaneous route, the most common protocol being two or three subcutaneous injections daily.…”

Section: Somatostatin Analogs In Oncologymentioning

confidence: 67%

Somatostatin analogs and radiopeptides in cancer therapy

Froidevaux¹,

Eberlé²

2002

Biopolymers

135

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Since the discovery of somatostatin (sst) in 1973, numerous chemical and biological studies have been carried out to develop sst analogs with enhanced resistance to proteases and prolonged activity. Three highly potent sst analogs-octreotide, lanreotide, and vapreotide-are now available in the clinic, and demonstrate efficacy in the treatment of tumors of the pituitary and the gastroenteropancreatic tract. The most striking effect is the control of hormone hypersecretion associated with these tumors. Available data on growth suppression in patients indicate a limited antiproliferative action, tumor shrinkage is observed in 10-20% patients, and tumor stabilization in about half of the patients for duration of 8-16 months. Eventually, however, all patients escape from sst analog therapy with regard to both hormone hypersecretion and tumor growth, the only exception being observed in acromegalic patients who do not experience tachyphylaxis even after more than 10 years of daily octreotide injection. The mechanism underlying the escape phenomenon is not yet clarified. Regarding the molecular mechanisms involved in sst antineoplastic activity, both indirect and direct effects via specific somatostatin receptors (SSTRs) expressed in the target cells have be described. Direct action may result from blockade of mitogenic growth signal or induction of apoptosis following interaction with SSTRs. Indirect effects may be the result of reduced or inhibited secretion of growth-promoting hormones and growth factors that stimulate the growth of various types of cancer; also, inhibition of angiogenesis or influence on the immune system are important factors. Five SSTR subtypes have been identified so far, which are variably expressed in a variety of tumors such as gastroenteropancreatic (GEP) tumors, pituitary tumors, and carcinoid tumors. Although all five SSTR subtypes are linked to adenylate cyclase, they are now known to affect multiple other cellular signaling systems and hence they differentially participate in the regulation of the various cellular processes. The finding of several laboratories that SSTR-expressing tumors frequently contain two or more SSTR subtypes, and the recent discovery that SSTR subtypes might form homo/heterodimers to create a novel receptor with different functional characteristics, expand the array of selective SSTR activation pathways and subsequent intracellular signaling cascades. This may lead to improved clinical protocols that take into account possible synergistic interactions between the SSTR subtypes present on the same cancer cell. Radiolabeled sst analogs, such as [(111)In]-[diethylenetriamine pentaacetic acid (DTPA)-D-Phe(1)]-octreotide (OcreoScan), have proved to be very useful for tumor scintigraphy and internal radiotherapy of SSTR overexpressing tumors. The recent introduction of the metal chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) considerably improved the stability of the radioconjugates, making possible the incorporation of a variety of radionuclide...

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Pharmacokinetic study and effects on growth hormone secretion in healthy volunteers of the new somatostatin analogue BIM 23014

Cited by 23 publications

References 28 publications

Pharmacokinetic and pharmacodynamic properties of a long‐acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.

Pharmacokinetic and pharmacodynamic properties of a long‐acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.

The efficacy and safety of lanreotide Autogel in patients with acromegaly previously treated with octreotide LAR

Somatostatin analogs and radiopeptides in cancer therapy

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