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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 Cmax on day 1 then elimination (apparent t1/2 25.5 days); 120-mgprofile was underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a Cmean of 1216 g/mL (range, 1065–1585) with low fluctuation index (43%). Steady-state PK of lanreotide 90 mg/28 d suggested a Cmean of 4455 g/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.