PHARMACOKINETIC AND PHARMACODYNAMIC PROPERTIES OF A LONG-ACTING FORMULATION OF THE NEW SOMATOSTATIN ANALOG, LANREOTIDE, IN NORMAL HEALTHY-VOLUNTEERS

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, fT4 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(-1) 2 h following injection. The levels then progressively decreased, remaining above 1.5 ng ml(-1) until day 11 and reaching 0.92 +/- 0.28 ng ml(-1) 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. fT4 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(-1) whereas plasma IGF-1 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-1 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.