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)

Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients

“…In agreement with other trials with lanreotide SR (16,22,25), we observed a small rise in fasting blood glucose during therapy, whereas others found no change in glucose metabolism (23). In our study, as well as in others (22,23), no obvious deterioration in glucose metabolism was seen in patients with overt diabetes.…”

“…By contrast, only 2 of 11 patients (18%) reached a normal IGF-I when the interval was further reduced from 10 to 7 days. This can be explained by the speci®c pharmacological pro®le of the drug reaching a maximum effect after 9 days: a mean IGF-I suppression of 80% at day 4, 83% at day 9 versus 53% at day 14 was obtained (16). This pro®le also explains why a further reduction of the dose interval from 10 to 7 days is less bene®cial.…”

Octreotide

“…A long-acting intramuscular formulation of lanreotide also controls growth hormone secretion in patients with acromegaly, but its duration of action is two weeks at most. 73 …”

The octreotide test dose is not a reliable predictor of the subsequent response to somatostatin analogue therapy in patients with acromegaly

“…Octreotide can control GH and insulin-like growth factor (IGF-1) secretion, on average, in approximately two-thirds of patients with acromegaly and, when used as primary therapy, it can induce significant tumour shrinkage in approximately 30% of patients (4,5). Lanreotide, an alternative SA of comparable potency, is available as twice-weekly or monthly preparations (4,6,7).…”