A comparison of continuous subcutaneous paliperidone infusion and repeated subcutaneous injection of risperidone free-base in rats.

It is proposed that to achieve a therapeutic effect in schizophrenia patients, dopamine D(2)-receptor occupancy by antipsychotics within the striatum must exceed 60-65%. However, at high levels of D(2)-receptor occupancy, the risk of extrapyramidal symptoms (EPS) is increased. Following oral dosing of antipsychotics, peaks and troughs in plasma drug concentrations may be mirrored by fluctuations in D(2)-receptor occupancy. Paliperidone, a novel antipsychotic available as extended-release tablets (paliperidone ER), is the major active metabolite of risperidone and exhibits a plasma pharmacokinetic profile with reduced peak-trough fluctuations and consistent D(2)-receptor occupancy compared with conventional oral antipsychotic formulations. Using formulations that resemble those in clinical practice, this study provides a preclinical evaluation of the pharmacological properties of paliperidone ER and risperidone immediate-release formulation in terms of consistent antipsychotic efficacy over time and extrapyramidal symptom liability. Significant fluctuations in inhibition of d-amphetamine-induced hyperlocomotion were observed for repeated subcutaneous (SC) risperidone injections, whereas stable inhibitory efficacy was demonstrated during continuous SC paliperidone infusion. Similarly, significant fluctuations in latency on-bar were observed with repeated SC risperidone injections, whereas significantly lower latency on-bar was demonstrated following continuous SC paliperidone infusion. These results in an animal model suggest that although risperidone and paliperidone demonstrate similar pharmacologic effects, continuous administration of paliperidone achieves more stable antipsychotic efficacy with reduced motor impairment, akin to the effects observed with paliperidone ER in clinical studies.

Role of rHuEpo on blood transfusions in preterm infants after the fifteenth day of life.

The specific aim of the study was to assess the safety and efficacy of recombinant human erythropoietin (rHuEpo) in reducing the need for blood transfusions in preterm infants after the 15th day of life. Between 1 October 1994 and 1 October 1995, 107 preterm infants, gestational age < or = 34 weeks, were admitted to the Neonatal Intensive Care Unit and received rHuEpo subcutaneously, 900 U/kg week-1, 3 times weekly, supplemented with iron and vitamin E. Treatment was started at 8 days of life and lasted from a minimum of 6 weeks to a maximum of 3 months. A total of 116 preterm infants of the same gestational age, admitted to the Neonatal Intensive Care Unit from 1 January 1992 to 31 December 1992, served as controls. Entry criteria were gestational age < or = 34 weeks and no major congenital malformation. There were no differences in routine care between the two groups. Hematological measurements and transfusion requirements were followed during therapy. The infants were divided into two groups according to birth weight (< 1500 g and > or = 1500 g), and for each group the number of patients who received blood transfusions and when blood transfusions occurred, before or after the 15th day of life, was recorded. There was a statistically significant difference only for transfusions carried out after the 15th day of life (p < 0.002). No adverse effects attributable to rHuEpo during the treatment were noted. The results indicate that early rHuEpo treatment, in combination with iron supplements, is effective in reducing the need for blood transfusions in preterm infants after the 15th day of life.

Yeast-derived hepatitis B vaccine in thalassaemic patients: a preliminary report.

Preliminary results of a trial involving a yeast-derived hepatitis B vaccine administered to 41 transfusion-dependent thalassaemic patients and 2 patients with spherocytosis are reported. Twenty-microgram doses of HBsAg were administered according to either a 0, 1, and 6 month or 0, 1, and 2 month schedule. Serum specimens collected prior to vaccination, one month after each vaccine dose, and again at 5 and 15 months, were tested for HBV markers and ALT. To date, seroconversion (anti-HBs titres greater than 10 IU/l) was observed in 15%, 67%, and 86% of patients one month following the three vaccine doses, respectively. Although the study is still in progress, a comparison of these results with those previously obtained using plasma-derived vaccine indicates that seroconversion to the recombinant yeast-derived vaccine is at least as high as that obtained by plasma-derived vaccines in patients affected by thalassaemia major.