Objective: To investigate the pharmacokinetic profile of a prolonged release, aqueous Autogel formulation of the somatostatin analogue lanreotide (Lan-ATG).
Design: A phase II, randomized, double-blind study, during which patients received 60, 90 or 120 mg Lan-ATG for four fixed administrations at 28-day intervals.
Patients: A total of 18 patients with acromegaly were recruited; six patients were randomized to each treatment.
Measurements: Lanreotide minimum concentration (C(min)), maximum serum concentration (C(max)) and area under the concentration-time curve during a dosing interval (AUC(tau)) were assessed after a single dose and at steady state (ss). Serum GH and IGF-1 levels were assessed before each administration and at the end of the study.
Results: After a single administration, dose proportionality for C(min,1), C(max) and AUC(tau) was demonstrated statistically. After repeated administrations, Lan-ATG exhibited linear pharmacokinetics over the dose range and ss values of C(min), C(max) and AUC(tau) increased in a dose-dependent, linear manner. Mean C(max,ss) values were only two- to fourfold greater than C(min,ss) values, and there was good control over the entire release profile. Serum levels of GH and IGF-1 declined over the course of the study and acromegaly symptoms improved. The treatment was well tolerated.
Conclusions: Lan-ATG showed linear pharmacokinetic profiles over the three dose levels after both single and repeated dosing, no initial burst effect and good control over the entire release profile. Despite the absence of dose adaptation, four injections of Lan-ATG were effective in lowering serum levels of GH and IGF-1.