Pharmacokinetics of SMS 201-995 in Healthy Subjects

Abstract

Kutz K, Nuesch E, Rosenthaler J. Pharmacokinetics of SMS 201-995 in healthy subjects.

The pharmacokinetics of a new somatostatin derivative, SMS 201-995, was investigated in a group of eight healthy subjects. SMS 201-995 was given intravenously in doses of 25 μg, 50 μg, 100 μg, and 200 μg and also subcutaneousIy in doses of 50 μg, 100 μg, 200 μg, and 400 μg in accordance with a randomized Latin-square design. Blood samples were taken up to 8 h. The tolerability of SMS 201-995 was very good. Routine blood chemistry variables remained normal. After intravenous administration of SMS 201-995 initial half-lives ranging from 9 ± 2 min to 14 ± 4 min and second half-lives of from 72 ± 22 min to 98 ± 37 min were calculated for the different doses. SMS 201-995 was rapidly absorbed after subcutaneous injection with a half-life ranging from 5.3 ± 2.2 min to 11.7 ± 7.6 min. The disposition half-life was from 88 ± 20 min to 102 ± 16 min for the different doses. Cp(tmax) and AUC (0 - ∞) increased dose-dependently after both routes of administration, pointing to linear pharmacokinetics for SMS 201-995. On the basis of its good tolerability, slow plasma clearance, and long action, SMS 201-995 represents a valuable tool for further clinical studies.

Key Words:

• Pharmacokinetics
• SMS 201-995
• somatostatin