Dihydroquinidine versus disopyramide: Efficacy in patients with chronic stable ventricular ectopy

Dihydroquinidine (DQ) is contained in substantial amounts in quinidine salts, but its direct antiarrhythmic action has not been studied. The efficacy of oral DQ (300 mg t. i. d.) compared to disopyramide (D) (200 mg t.i.d.) was thus investigated using a double-blind crossover placebo-controlled protocol in 12 patients, aged 13 to 67 years, with chronic stable high frequency premature ventricular beats (PVB), defined as greater than 100 PVB/h during 48-72-h control Holter monitoring. The protocol included three 72-h treatment periods: DQ, D, and placebo at random. On days 2 and 3 of each period a 24-h Holter recording was carried out; drug blood levels were determined at peak (days 2 and 3) and trough time (day 3). No significant difference in the mean PVB/h was found between control (735 +/- 400) and placebo periods (564 +/- 388), or between the two Holter recordings of each period. Compared to placebo both DQ (106 +/- 113, p less than 0.005) and D (240 +/- 263, p less than 0.05) reduced the mean PVB/h, but the decrease was significantly higher with DQ (78 versus 53%, p less than 0.02). Nine patients (75%) on DQ and 5 (42%) on D had a greater than 70% decrease in mean PVB/h; complex PVBs were abolished in 3 of 6 patients on both treatments. On day 3, DQ plasma levels were 1.31 +/- 0.44 (peak) and 0.92 +/- 0.45 (trough) mg/l; D plasma levels were 2.88 +/- 0.64 (peak) and 2.02 +/- 0.31 (trough) mg/l; no significant difference was found between day 2 and day 3 samples.(ABSTRACT TRUNCATED AT 250 WORDS

Nitrate plasma level as a marker of nitric oxide production after subcutaneous interleukin 2 immunotherapy

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Intravenous (iv) or Oral (os) Busulphan (BUS) in Children Prior to Autologous (Auto) or Allogeneic (Allo) Stem Cell Transplantation (SCT): Pharmacokinetics (PK), Toxicity and Compliance.

Introduction: High dose BUS is an important component of pre-transplant conditioning regimen in children with advanced hematological malignancies or solid tumor undergoing allogeneic or autologous stem cell transplantation. Variable intra and inter systemic drug exposure as measured by area under curve (AUC), can occurs following oral administration and may be influenced by age, body weight, absorption variability and, particularly in infants, by difficulties to assumption. Aims: to compare the PK, the toxicity and the compliance of iv versus oral BUS administration in children undergoing pre-transplant conditioning regimen. Patients and methods: 12 patients (pts), median age 37 (7\u2013177) mos, body weight 6\u201369 kg, affected by AML (3), ALL (4), NB (3), Thalassemia (2), undergoing to autoSCT (4) or alloSCT (8), received as preparative regimen oral BUS at the dose of 1 mg/kg every 6 hours for a total of 16 doses (6 pts, GR1), or 2 hours i.v. infusion of BUS at the dose of 0.8 mg/kg every 6 hours for a total of 16 doses (6 pts, GR2). Four out of 6 GR1 pts (7\u201330 mos) had a nasogastric radiolus to allow BUS assumption. PK studies were performed after the first dose of BUS on blood samples collected at 0, 1, 2, 4, 6 hours after first administration in GR1 and at 0, 2, 3, 4, 6 hours from the beginning of the first infusion in GR2. BUS plasma level was determined by high-performance liquid chromatography as described by Henner et al. Results: GR were comparable as for age (p= 0.07) and body weight (p= 0.14). Comparison of PK median values (+SD) in GR1 versus GR2 didn\u2019t highlighted statistically significant differences as for AUC (p= 0.20) and for T1/2 (p= 0.11). Peak concentration was higher in GR2 (p= 0.058). Bioavailability was 0.61. Variation factor (VF%) were constantly low in GR2. No pt showed acute or late treatment-related extra-medullary toxicity and all pts developed a rapid and sustained hematopoietic recovery. Conclusions: systemic exposure to 0.8 mg/kg iv BUS versus 1 mg/kg oral BUS is overlapping. Low VF% highlight a smaller interpatient variability in exposure compared to oral BUS. Moreover allows to avoid assumption difficulties in younger pts