A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly.
We investigated the pharmacokinetics of bromocriptine and octreotide, both individually and in combination, in 12 patients with active acromegaly. The pharmacodynamics of the drugs were assessed by 12-h profiles of GH secretion and insulin-like growth factor-I (IGF-I) measurements. During the 42-day study period, bromocriptine was administered for 28 days (from day 8; 5 mg, orally, twice daily) and octreotide (200 micrograms, sc, twice daily) from days 15-42. IGF-I levels, 12-h GH, and plasma bromocriptine and octreotide profiles were obtained on days 0, 14, 28, and 42. During bromocriptine treatment, both the area under the GH day curves (AUC) and mean IGF-I decreased to 64% (95% confidence limits, 43-72% and 48-82%, respectively) of initial values. During octreotide treatment, the respective values were 23% (18-30%) and 32% (21-36%), which were greater decreases than those during bromocriptine treatment [36% (95% confidence limits, 32-54%) for AUC for GH and 50% (95% confidence limits, 34-58%) for IGF-I]. With combined treatment, the AUC for GH was reduced to 16% (12-21%) and that of IGF-I to 25% (16-27%) of initial values. This combination was more effective than bromocriptine [25% (95% confidence limits, 22-37%) for AUC for GH and 39% (95% confidence limits, 25-43%) for IGF-I] and octreotide alone [78% (95% confidence limits, 53-89%) for AUC for GH and 78% (95% confidence limits, 57-98%) for IGF-I]. The pharmacokinetic parameters of octreotide were unchanged by the coadministration of bromocriptine. The bioavailability of bromocriptine increased by approximately 40% when bromocriptine was administered together with octreotide compared with administration alone (P < 0.01). Bromocriptine disposition parameters were unaltered. In conclusion, treatment of acromegalics with a combination of octreotide and bromocriptine increases the bioavailability of bromocriptine and reduces both GH and IGF-I levels more effectively than treatment with either drug alone. This presents the possibility of less frequent drug administrations, lower doses of octreotide, and, consequently, lower treatment costs.
Fløgstad
A K
AK
Medical Department B, Rikshospitalet, National Hospital, Oslo, Norway.
Halse
J
J
Grass
P
P
Abisch
E
E
Djøseland
O
O
Kutz
K
K
Bodd
E
E
Jervell
J
J
D000172:Acromegaly / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D001682:Biological Availability; D001971:Bromocriptine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D001971:Bromocriptine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide