Pharmacokinetics and efficacy of the long-acting somatostatin analogue somatuline in acromegaly.
The aim of this work was to assess the use of a sustained-release formulation of somatuline, a long-acting analogue of somatostatin, in the treatment of acromegaly. Fifteen patients with active acromegaly, as defined by random growth hormone (GH) levels greater than 10 mU/l, which fail to be suppressed to less than 5 mU/l following an oral glucose load, were studied. Somatuline was administered as an intramuscular injection in two regimens: eight patients were given a single injection of the sustained-release formulation and blood samples taken over the next month for the measurement of both basal levels of GH and the GH response to thyrotrophin-releasing hormone; and eight patients were given injections of the sustained-release formulation at 2-week intervals over a 6-month period and basal plasma GH levels and the GH response to both an oral glucose load and to thyrotrophin-releasing hormone was assessed. Following a single intramuscular dose of the sustained-release preparation, random GH levels were reduced to below 10 mU/l in five patients and by greater than 50% of basal levels in the remainder. The insulin-like growth factor I (IGF-I) levels fell to within the normal range in three patients. In the long-term efficacy study. GH levels were reduced to < 10 mU/l in 7/8 patients. The IGF-I levels were normalized in four patients. Five of the eight patients experienced diarrhoea, two of mild and three of moderate severity; none of the patients withdrew from the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
M R
MR
Department of Medicine, Bristol Royal Infirmary, UK.
Chowdrey
H S
HS
Thomas
F
F
Grint
C
C
Lightman
S L
SL
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000592:standards; D010456:Peptides, Cyclic; D013004:Somatostatin / Q000031:analogs & derivatives*
D003692:Delayed-Action Preparations; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose; D015282:Octreotide