title: A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly.
abstract: 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.
authors.affiliation: Medical Department B, Rikshospitalet, National Hospital, Oslo, Norway.
authors.forename: A K
authors.initials: AK
authors.lastname: Fløgstad
authors.forename: J
authors.initials: J
authors.lastname: Halse
authors.forename: P
authors.initials: P
authors.lastname: Grass
authors.forename: E
authors.initials: E
authors.lastname: Abisch
authors.forename: O
authors.initials: O
authors.lastname: Djøseland
authors.forename: K
authors.initials: K
authors.lastname: Kutz
authors.forename: E
authors.initials: E
authors.lastname: Bodd
authors.forename: J
authors.initials: J
authors.lastname: Jervell
mesh_terms: 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*
chemical_list: D001971:Bromocriptine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide