Endocrine profile of a long-acting somatostatin derivative SMS 201-995. Study in normal volunteers following subcutaneous administration.
The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201-995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 micrograms. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 micrograms of SMS 201-995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P less than 0.001 and P less than 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P less than 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P less than 0.001) inhibited by previous sc injection of 50 micrograms of SMS 202-995. Pretreatment with 50 and 100 micrograms of SMS 202-995 sc (n = 9) inhibited (P less than 0.001) the stimulatory effect of TRH (200 micrograms iv) on TSH without modifying basal levels. The injection of 100 micrograms/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials. Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
del Pozo
E
E
Neufeld
M
M
Schlüter
K
K
Tortosa
F
F
Clarenbach
P
P
Bieder
E
E
Wendel
L
L
Nüesch
E
E
Marbach
P
P
Cramer
H
H
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D015282:Octreotide; D012890:Sleep / Q000502:physiology; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D001786:Blood Glucose; D004044:Dietary Proteins; D007328:Insulin; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D005934:Glucagon; D001120:Arginine; D015282:Octreotide