Pharmacokinetic profile of lanreotide Autogel in patients with acromegaly after four deep subcutaneous injections of 60, 90 or 120 mg every 28 days.

OBJECTIVE: To investigate the pharmacokinetic profile of a prolonged release, aqueous Autogel formulation of the somatostatin analogue lanreotide (Lan-ATG). DESIGN: A phase II, randomized, double-blind study, during which patients received 60, 90 or 120 mg Lan-ATG for four fixed administrations at 28-day intervals. PATIENTS: A total of 18 patients with acromegaly were recruited; six patients were randomized to each treatment. MEASUREMENTS: Lanreotide minimum concentration (C(min)), maximum serum concentration (C(max)) and area under the concentration-time curve during a dosing interval (AUC(tau)) were assessed after a single dose and at steady state (ss). Serum GH and IGF-1 levels were assessed before each administration and at the end of the study. RESULTS: After a single administration, dose proportionality for C(min,1), C(max) and AUC(tau) was demonstrated statistically. After repeated administrations, Lan-ATG exhibited linear pharmacokinetics over the dose range and ss values of C(min), C(max) and AUC(tau) increased in a dose-dependent, linear manner. Mean C(max,ss) values were only two- to fourfold greater than C(min,ss) values, and there was good control over the entire release profile. Serum levels of GH and IGF-1 declined over the course of the study and acromegaly symptoms improved. The treatment was well tolerated. CONCLUSIONS: Lan-ATG showed linear pharmacokinetic profiles over the three dose levels after both single and repeated dosing, no initial burst effect and good control over the entire release profile. Despite the absence of dose adaptation, four injections of Lan-ATG were effective in lowering serum levels of GH and IGF-1.

Efficacy and tolerability of the long-acting somatostatin analog lanreotide in acromegaly. A 12-month multicenter study of 58 acromegalic patients. French Multicenter Study Group on Lanreotide in Acromegaly.

OBJECTIVE: To determine the effects of the new somatostatin analogue, lanreotide, in its prolonged released form (PR), in patients with acromegaly. DESIGN: Prospective open multicenter non comparative study. SETTING: Thirty-three university-affiliated medical centers. PATIENTS: One hundred sixteen acromegalic patients with active disease, of whom 58 patients complied with the protocol and completed the 12-month period treatment. INTERVENTION: Lanreotide PR treatment was started at a dose of 30 mg intramuscularly every 14 days. If integrated mean plasma GH levels were not below 5 micrograms/L and/or IGF-I levels were not normalized after one month of treatment, injections were given every 10 days. The duration of the study was 12 months. RESULTS: After one month of treatment mean plasma GH and IGF-I levels had fallen from 10.7 +/- 11.1 micrograms/L (mean +/- SD; range, 2.6-74.8 micrograms/L; median, 7 micrograms/L) and 718 +/- 270 micrograms/L (range 338-1440 micrograms/L; median, 645 micrograms/L), respectively, to 7.8 +/- 10.1 micrograms/L and 575 +/- 252 micrograms/L, respectively. Thirty patients (22%) had plasma GH levels below 2.5 micrograms/L, and 8 patients (16%) had age-adjusted normal plasma IGF-I levels. At the sixth month of treatment mean plasma GH levels of 2.5 micrograms/L or less, and normal plasma IGF-I levels were observed in 33%, and 33% of patients, respectively. At the twelvth month of treatment, these percentages were 41%, and 41%, respectively. The interval between two injections was shortened (one injection every 10 days) in 8 of the 58 patients (13%) at the second month of treatment, and at the end of the study, 70% of patients required 3 injections per month. The most frequent adverse event elicited by enquiry was transient diarrhea (76% of patients), followed by abdominal pain (62%) and pain at the injection site (59%). Based on the analysis of a subgroup of 46 patients who had at least a measurement of fecal fat content after day 0 of the study, a non significant increase (from 4.2 +/- 3.4 to 5.1 +/- 4.3 g/24 h, p = 0.3) in mean steatorrhea was observed during treatment. Before treatment, steatorrhea was present in 9 (19%) patients. During the study, 15 additional patients (32%) developed persistent steatorrhea, and there was a transient increase in fecal fat content above 6 g/24 h in another 11 patients. After exclusion of the 7 patients (12%) with gallstones at enrollment, new gall-stones were diagnosed in 6 out of 50 patients (12%) during the study. CONCLUSION: Two or three monthly injections of lanreotide PR decreased GH concentration to less than 2.5 micrograms/L and normalized IGF-I levels in 41% of patients treated during 12 months. The good tolerability of this treatment, and the reduction in the frequency of injections, plus the sustained drug serum concentrations, confirm the usefulness of this new somatostatin analog formulation.

Toxoplasma pericarditis in acquired immunodeficiency syndrome.

Large pericardial effusions are now a well-known complication of the acquired immunodeficiency syndrome, mainly caused by mycobacterial disease. However, other etiologies can be found. We report a case of toxoplasma pericarditis without other parasitic localizations. Pericarditis is a very uncommon clinical feature during toxoplasmosis. Its diagnosis is often difficult to establish, particularly in immunocompromised patients. Nevertheless, its possible evolution to constriction or tamponade requires its consideration. New methods of rapid tissue cultures may be helpful and allow early specific treatment.