Treatment with octreotide and bromocriptine in patients with acromegaly: an open pharmacodynamic interaction study.
OBJECTIVE
Several studies suggest that the combination of octreotide and bromocriptine is more effective than octreotide alone in reducing GH levels in patients with acromegaly. However, these studies have evaluated either the acute effects of single doses of octreotide and bromocriptine, or the effects of long-term combination therapy, in which octreotide was given only twice a day. The aim of the study was to evaluate the effects of the combination of octreotide and bromocriptine compared to octreotide alone, using a treatment scheme of three daily injections of octreotide during a period long enough to ensure a pharmacokinetic and pharmacodynamic steady state.


METHODS
Eleven patients with acromegaly.


METHODS
Different treatment regimes were performed during three periods. During the first period there was no administration of octreotide or bromocriptine, during the second period 100 micrograms octreotide was given subcutaneously three times a day, and during the third period 100 micrograms octreotide was given subcutaneously three times a day in combination with bromocriptine, given orally 5 mg twice daily. When the patients were without any treatment a single oral dose of 5 mg bromocriptine was given at 0730 h. Individual GH levels were assessed as the mean value of 11 observations during the day, at hourly intervals from 0730 to 1530 h, and at 1730 and 1930 h, and the GH levels for the whole group were calculated as the mean of the individual mean values. Serum IGF-I and PRL were measured in fasting samples at 0730 h on the same days as GH, GH, IGF-I, and PRL were evaluated at the end of each treatment regime.


RESULTS
Basal mean GH value for all 11 patients was 54.2 +/- 17.4 mU/l. During octreotide therapy mean GH value was significantly reduced compared to basal mean GH level; 19.86 +/- 6.82 mU/l (P < 0.05). The reduction of mean GH during combination therapy was also significant compared to basal, 18.70 +/- 6.72 mU/l (P < 0.05). Basal mean IGF-I value for all 11 patients was 716 +/- 96 micrograms/l. During octreotide therapy mean IGF-I value was significantly reduced compared to basal mean IGF-I level; 458 +/- 100 micrograms/l (P < 0.05). The reduction of mean IGF-I during combination therapy was also significant compared to basal, 456 +/- 93 micrograms/l (P < 0.05). There was no difference between the levels of mean IGF-I during the two treatment periods. One patient, the only patient with hyperprolactinaemia, showed an additional reduction of GH levels of > 50% during combination therapy. This was also the patient showing the most pronounced reduction of GH levels after the administration of a single dose of bromocriptine.


CONCLUSIONS
When octreotide is administered three times a day, the additive effect of bromocriptine on GH and IGF-I suppression seems to be negligible in most patients with acromegaly.
Fredstorp
L
L
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Kutz
K
K
Werner
S
S
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D001971:Bromocriptine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage*
D001971:Bromocriptine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide