Follow-up study of patients treated with olanzapine pamoate in France in real-life treatment situation.

OBJECTIVE: To characterize patients treated with olanzapine pamoate in French centers and investigate the conditions of use of olanzapine pamoate in real-life treatment situation. METHODS: Data came from French sites participating in an international post-authorization safety study. In this observational study, patients diagnosed with schizophrenia were receiving commercially available olanzapine pamoate, in accordance with their physician's usual standard of care. Data were collected during routine visits within the standard course of patient care. RESULTS: One hundred and thirty eight patients (male, 73.9%; mean age, 39.4 years; mean duration of disease, 12.7years) received olanzapine pamoate and were included in the study by 32 investigative psychiatrists distributed across 20 different sites (psychiatric hospitals). During the period of analysis, a total of 2975 injections of olanzapine pamoate was administered to the patients. The mean duration of olanzapine pamoate exposure was 475 days (1.3years). During follow-up, 13.8% of all patients had at least one psychiatric hospitalization, 15.9% had at least one same-day psychiatric hospitalization (information documented for 116patients), and 44.2% received at least one concomitant drug. Three cases of post-injection delirium/sedation syndrome were reported during the analysis period. Treatment emergent adverse events (incidence, 20.3%) were in line with the known profile of olanzapine. CONCLUSION: Patients were administered olanzapine pamoate and monitored in compliance with label recommendations. The safety profile assessment of olanzapine pamoate in actual conditions was consistent with that described in clinical studies.

Bradykinin B2 receptor involvement in rabbit and murine models of septic shock.

The purpose of our work was to evaluate the role of bradykinin B2 receptors in the early phase (first 3 h) of bacterial lipopolysaccharide (LPS)-induced shock in anesthetized and mechanically ventilated rabbits and to determine if HOE 140, a specific, potent, and long-acting bradykinin B2-receptor antagonist, could improve survival in two murine models of septic shock. In rabbits, LPS injection induced rapid hypotension associated with metabolic acidosis. Three hours after the injection of LPS, we observed leukopenia, thrombocytopenia, and a moderate increase in arterial blood cyclic GMP. The injection-of HOE 140 [1.7-mumol/kg bolus intravenously (i.v.) 20 min before LPS] inhibited the decrease in blood pressure, but did not influence any of the other parameters studied. Mice were subjected to intraperitoneal (i.p.) injection of LPS, which induced almost 100% mortality in the 4 days after the injection. Pretreatment with HOE 140 (1 mg/kg i.p.) 30 min before the LPS injection and 4, 8, and 24 h afterward the injection did not improve survival at any given time during the 4 days of the study. Cecal ligation and puncture in mice induced a mortality rate > 90% in < or = 10 days. HOE 140 (1 mg/kg i.v.) given 30 min before cecal ligation did not significantly improve the survival rate. In contrast with previous reports, in the present study in a rabbit model of endotoxic shock (early phase) and in two murine models of septic shock, the involvement of bradykinin B2 receptors appeared to be minimal.

Effects of the bradykinin B2 receptor antagonist S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) in different in vivo animal models of inflammation.

The effects of S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (BK)], a new, potent and long-acting BK B2 antagonist, were tested in some in vivo models of inflammation. In rats, S 16118 (0.1 and 1 mg/kg) given i.v. or s.c. delayed the edema formation induced by intraplantar carrageenan injections up to 4 hr after administration, confirming the involvement of kinins in this inflammatory reaction. In guinea pigs treated with atropine, vagal stimulation induced bronchial microvascular leakage. Aerosolization of S 16118 (5 x 10(-3) M for 20 sec), 4 min before vagus nerve stimulation, induced a 60% decrease in the Evans blue extravasation, demonstrating the modulatory role of BK in neurogenic inflammation. In rats, caerulein infusion (4 nmol/kg/hr) induced hypotension, massive pancreatic edema, hypovolemia due to plasma leakage and an increase in serum lipase and amylase activity. S 16118 (100 nmol/kg s.c.) prevented the hypotension, the pancreatic edema and the hypovolemia and induced a marked increase in the serum lipase and amylase activity. This confirms that BK, acting on BK B2 receptors, is involved in this model of pancreatitis. In rabbits, the injection of lipopolysaccharides (LPS; 600 micrograms/kg i.v.) induced hypotension, metabolic acidosis and leukopenia. S 16118 (1.73 mumol/kg i.v.) did not influence the effects of LPS injection. In mice, i.p. LPS (25 mg/kg) administration induced over 90% mortality in 96 hr. S 16118 (1 mg/kg x 4), given 30 min before LPS injection and 4, 8 and 24 hr after LPS injection, did not influence the mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)