Pharmacokinetics of the long-acting somatostatin analogue octreotide (SMS 201-995) in acromegaly.
A single-dose study was performed to examine the pharmacokinetics of subcutaneous octreotide in acromegalic patients and to investigate the relationship between growth hormone and the elimination half-life of the drug. Fourteen acromegalic patients (six men and eight women; age range 35-59 years) who had previously received conventional treatment were studied. Two subjects were on long-term octreotide which had been discontinued 72 h before the study. Octreotide 100 micrograms was administered subcutaneously and plasma samples taken every 10 min for 1 h and then hourly for up to 8 h. Growth hormone was measured at 0, 2 and 8 h. Octreotide was rapidly absorbed with a mean (+/- SEM) t1/2abs of 5.4 min (+/- 0.8) peaking at a mean plasma concentration of 3.4 nmol/l (+/- 0.2) in 27.4 min (+/- 3.7). The monoexponential elimination phase had a mean half-life of 110 min (+/- 9.6). The apparent volume of distribution was 29.4 1 (+/- 1.9) and total clearance was 172 ml/min (+/- 10.4). These results were similar to those obtained in normal volunteers. There was no simple relationship between the level of growth hormone and the half-life of octreotide. Growth hormone levels ranged from 2.5 to 34.0 mIU/l but were only greater than 10 mIU/l in three subjects. Further studies of octreotide pharmacokinetics are needed in untreated patients with acromegaly with raised growth hormone levels.
Nicholls
J
J
Department of Pharmacy, Hammersmith Hospital, London.
Wynick
D
D
Domin
J
J
Sandler
L M
LM
Bloom
S R
SR
D000172:Acromegaly / Q000378:metabolism*; D000328:Adult; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000493:pharmacokinetics*; D011863:Radioimmunoassay
D013006:Growth Hormone; D015282:Octreotide