title: Pharmacokinetics and efficacy of a long-acting formulation of the new somatostatin analog BIM 23014 in patients with acromegaly.
abstract: The treatment of acromegalics with somatostatin analogs requires continuous sc infusion using pumps or several sc injections daily. Long-acting formulations (BIM-LA) of BIM 23014 (BIM) using delayed microcapsules may provide a more convenient form of therapy. Fourteen acromegalics whose GH secretion had not been normalized by transphenoidal surgery followed, in 10 cases, by pituitary radiotherapy (performed at least 2 yr before the study) were studied. Eight of these patients participated in an initial study of the pharmacokinetics of BIM-LA, after which a 6-month efficacy study was undertaken. The 8 patients in the pharmacokinetic study had an initial blood sample collected for measurements of plasma GH and insulin-like growth factor-I (IGF-I) levels before the im injection of 30 mg BIM-LA, and blood samples were subsequently taken 2, 4, 6, and 8 h after injection and then twice a week for a month. Plasma IGF-I levels were measured on days 4, 14, 20, and 30 after the injection. Assays of plasma GH, IGF-I, and BIM levels were performed by RIAs. The results showed that plasma GH levels were markedly reduced from 26.0 +/- 2.0 to 2.5 +/- 0.2 micrograms/L 2 h after BIM-LA injection and remained lower than 5 micrograms/mL for the 11 following days. Plasma GH levels increased to 5.5 +/- 1.2 micrograms/L on day 14 and returned to basal values 23 days after injection. Similarly, plasma IGF-I decreased from an initial level of 656 +/- 43 to 324 +/- 23 ng/mL on day 4 and remained close to the normal range for the following 10 days. Plasma BIM levels reached a peak 2 h after the injection (7.2 +/- 2.3 ng/mL) and remained higher than or close to 1 ng/mL until the 14th day after injection. This initial study showed that a single injection of 30 mg BIM-LA effectively suppressed GH and IGF-I secretion for at least 14 days, in accordance with the kinetics of the drug in plasma. Based on the results of this initial study, 30 mg BIM-LA were injected twice monthly for 6 months in all 14 patients. All of the subjects had a basal evaluation before treatment with BIM-LA and were then subjected to assessment of clinical, pituitary, and hormonal parameters. Patients were evaluated after 3 and 6 months of treatment on the same basis as that previously used when starting the BIM-LA therapy. Plasma BIM levels were measured monthly. Clinical signs of acromegaly improved during the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Endocrinology, University of Rouen, Hopital de Bois Guillaume, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Heron
authors.forename: F
authors.initials: F
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Dero
authors.forename: A
authors.initials: A
authors.lastname: Gancel
authors.forename: J M
authors.initials: JM
authors.lastname: Ruiz
authors.forename: B
authors.initials: B
authors.lastname: Schatz
authors.forename: J M
authors.initials: JM
authors.lastname: Kuhn
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin