Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Ipsen Limited, 190 Bath Road, Slough, Berkshire, SL1 3XE, UK
Pharmacotherapeutic group: Antigrowth hormones
ATC code: H01CB03
Lanreotide is an octapeptide analogue of natural somatostatin. Like somatostatin, Lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine and paracrine functions. Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR1, 3, and 4. Activity at human SSTR 2 and 5 is the primary mechanism believed responsible for GH inhibition.
Lanreotide, like somatostatin, exhibits a general exocrine anti-secretory action. It inhibits the basal secretion of motilin, gastric inhibitory peptide and pancreatic polypeptide, but has no significant effect on fasting secretin or gastrin secretion. Lanreotide markedly inhibits meal-induced increases in superior mesenteric artery blood flow and portal venous blood flow. Lanreotide significantly reduces prostaglandin E1-stimulated jejunal secretion of water, sodium, potassium and chloride. Lanreotide reduces prolactin levels in acromegalic patients treated long term.
Lanreotide is clearly more active than natural somatostatin and shows a much longer duration of action.
A randomised, placebo controlled study has investigated the effects of lanreotide LA 30 mg administration every 10 days in 80 patients with inoperable upper intestinal obstruction of malignant origin due to confirmed peritoneal carcinomatosis. The primary objective was to assess the proportion of responders 7 days after a single injection of lanreotide LA 30 mg versus placebo. Treatment response was defined as 1 or less vomiting episode per day for at least 3 consecutive days, or no vomiting recurrence for at least 3 consecutive days for subjects in whom a nasogastric tube had been removed.
In the Intent-to-Treat [ITT] population (43 in the lanreotide group and 37 in the placebo group), when based on subject diary record cards (DRC) assessed at day 7, the responders rate was more favourable for lanreotide than placebo, although not statistically significant (41.9% [18/43] versus 29.7% [11/37], odds ratio=1.75 [95% CI 0.68-4.49, p=0.24]). When based on investigators assessment, there was a statistically significant difference in the responders rate in favour of lanreotide versus placebo in this population (50.0% [19/38] and 28.6% [10/35], respectively [odds ratio=2.82, 95% CI 1.00-7.86, p=0.048]).
Intrinsic pharmacokinetic parameters of lanreotide after intravenous administration in healthy volunteers indicated limited extravascular distribution, with a steady-state volume of distribution of 16.1 L. Total clearance was 23.7 L/h, terminal half-life was 1.14 hours and mean residence time was 0.68 hours.
In studies evaluating excretion, less than 5% of lanreotide was excreted in urine and less than 0.5% was recovered unchanged in faeces, indicating some biliary excretion.
The plasma profile of a single dose of Somatuline LA 30 mg administered intramuscularly in healthy volunteers is characterised by an initial rapid release phase, corresponding to the release of peptide bound to the surface of the microspheres, and then by a second release phase, followed by a very slow decrease induced by the prolonged release of the active substance captured in the microparticles constituting the drug product.
After an initial serum concentration peak of 8.5 ± 4.7 ng/mL obtained between 1 and 2 h after drug administration, serum levels decrease during 1-3 days and then rise from day 3 to 5 until day 14-21 showing a “pseudo plateau” with most of the serum levels around 1ng/mL during this period of time.
This prolonged release behaviour is described by a mean residence time of 15.0 ± 1.6 days and a half-life of 5.0 ± 2.3 days.
The pharmacokinetic profile in acromegalic patients after a single administration of Somatuline LA is comparable to that obtained in healthy volunteers.
Pharmacokinetic profile after repeated administration has also been studied in acromegalic patients. Steady state levels is obtained after the 4th consecutive dose presenting a peak of 10.9 ± 4.4 ng/mL around 2 hours after administration and then a “pseudo plateau” followed by a first order kinetics. The mean minimum and average serum concentrations at steady state is 2.2 ± 0.7 and 2.8 ± 0.8 ng/mL respectively and a no relevant accumulation is observed (Rac = 2.2).
Subjects with severe renal impairment show an approximately 2-fold decrease in total serum clearance of lanreotide, with a consequent increase in half-life and AUC. In subjects with moderate to severe hepatic impairment, a reduction in clearance was observed (30%). Volume of distribution and mean residence time increased in subjects with all degrees of hepatic insufficiency.
It is not necessary to alter the starting dose in patients with renal or hepatic impairment, as lanreotide serum concentrations in these populations are expected to be well within the range of serum concentrations safely tolerated in healthy subjects.
Elderly subjects show an increase in half-life and mean residence time compared with healthy young subjects. It is not necessary to alter the starting dose in elderly patients, as lanreotide serum concentrations in this population are expected to be well within the range of serum concentrations safely tolerated in healthy subjects.
In carcinogenic bioassays studies conducted in rats and mice, no systemic neoplastic changes were observed at doses in excess of those achieved in humans at therapeutic doses. Increased incidence of subcutaneous tumours were observed at the injection sites likely due to the increased dose frequency in animals (daily) compared to monthly dosing in humans and therefore may not be clinically relevant.
In in vitro and in vivo standard battery tests, lanreotide did not show any genotoxic potential.
Resorption of micropheres is completed in 45-60 days.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
