Long‐Acting Octreotide and Prolonged‐Release Lanreotide Formulations Have Different Pharmacokinetic Profiles

Abstract

Single-dose pharmacokinetic (PK) profiles and multiple-dose PK modeling were compared for long-acting octreotide (20 or 60 mg) and prolonged-release lanreotide (90 or 120 mg) over 91 days; steady-state profiles were simulated. All treatments were well tolerated. Octreotide 20-mg profile showed increased concentration on day 1, lag from days 2 to 6, then prolonged plateau phase (days 11-41); 60-mg PK was dose proportional. Lanreotide 90-mg profile showed C(max) on day 1 then elimination (apparent t1/2 25.5 days); 120-mg profile was underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a C(mean) of 1216 rhog/mL (range, 1065-1585) with low fluctuation index (43%). Steady-state PK of lanreotide 90 mg/28 d suggested a C(mean) of 4455 rhog/mL (range, 2499-9279) with high fluctuation index (152%). Long-acting octreotide had more predictable PK than prolonged-release lanreotide. Simulated steady-state profiles suggest long-acting octreotide could be optimized to meet individual patient needs. In contrast, prolonged-release lanreotide requires exposure constantly above the therapeutic target to enable monthly long-term therapy.

Treatment with Octreotide Does Not Reduce Tumor Uptake of 68Ga-DOTATATE as Measured by PET/CT in Patients with Neuroendocrine Tumors

“…The dissociation between receptor expression and internalization might be explained by another animal study, in which octreotide medication induced rapid SSTR subtype 2 internalization within 2.5 min in vivo, followed by recovery of receptor expression within 24 h (17). With the long-acting octreotide, the serum concentration remains quite stable over 28 d (18), as might be expected to result in concomitant receptor internalization and overexpression. This stability, however, need not also hold true for other somatostatin analogs such as lanreotide, for which the serum concentration decreases over time (18).…”

“…With the long-acting octreotide, the serum concentration remains quite stable over 28 d (18), as might be expected to result in concomitant receptor internalization and overexpression. This stability, however, need not also hold true for other somatostatin analogs such as lanreotide, for which the serum concentration decreases over time (18).…”

Preoperative octreotide treatment of acromegaly: long-term results of a randomised controlled trial

“…Particularly octreotide but also lanreotide has been proven to have a long biological half-life when given in slow-release formulas, and can be detected in circulation many weeks after injection (20,21). A phase I study demonstrated that the concentration of octreotide LAR decreases slowly to immeasurable values in the first 11 weeks after a single injection (22). A clinical study of SSA withdrawal has demonstrated suppressed hormone levels for several months in some patients (23).…”

Successful Management of Recurrent Neuroendocrine Carcinoma of the Sphenoid Sinus Using Octreotide LAR: A Case Report

“…Stable compound such as OCT LAR is now available for a convenient monthly injection and improves patient compliance. Prolonged drug release of OCT LAR is achieved by encapsulation in microspheres composed of a tumor [10]. Fluctuation of blood drug level may be seen in the initial 7-14 days.…”