The effect of mild and moderate renal impairment on the pharmacokinetics of pridopidine, a new drug for Huntington's disease.

AIM: Pridopidine, a new oral drug for treatment of patients with motor symptoms associated with Huntington's Disease (HD) is currently under development. In steady-state conditions, pridopidine elimination is mediated primarily through renal excretion. This study evaluated single dose and steady-state pharmacokinetics (PK) of a daily dose of pridopidine in subjects with mild and moderate renal impairment and matched healthy subjects. METHODS: Subjects with mild renal impairment (n = 12), moderate impairment (n = 12), or their matched healthy controls (n = 25) participated in this study. Subjects received a single dose of pridopidine (45 mg) on day 1 and a multiple dose cycle of 45 mg once daily on days 5-18. Blood and urine samples were collected on days 1 and 18 for PK analysis. RESULTS: Mild renal impairment did not affect the PK of pridopidine whilst an increase in exposure was seen in subjects with moderate renal impairment. Subjects with moderate impairment showed reduced plasma clearance (by 44%) and had 68% higher AUC (90% CI 1.22, 2.30) and 26% higher Cmax (90% CI 1.02, 1.56) values than those with normal renal function at steady-state. Pridopidine was safe and well tolerated in healthy subjects and in subjects with mild and moderate renal impairment. CONCLUSIONS: Mild renal impairment has no impact on exposure to pridopidine while moderately impaired renal function resulted in higher pridopidine concentrations.

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction. Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial.

BACKGROUND: Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. METHODS: We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI ( ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti- Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. RESULTS: There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG kappa = 0.611 (95% CI = 0.498-0.724, p < 0.001) and for IgA kappa = 0.431 (95% CI: 0.322-0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti- C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). CONCLUSION: Depending on the test system used, there are large differences in the prevalence of anti- C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.

The impact of different intensities of regular donor plasmapheresis on humoral and cellular immunity, red cell and iron metabolism, and cardiovascular risk markers.

BACKGROUND AND OBJECTIVES: Major studies are still lacking on the impact of differing intensities of long-term donor plasmapheresis, not only on total serum protein, albumin and immunoglobulin G (IgG), but also on humoral and cellular immunity, red cell and iron metabolism, and biochemical cardiovascular risk markers. MATERIALS AND METHODS: Three groups of donors, comprising 483 individuals undergoing differing intensities of long-term serial plasmapheresis, were entered into a cross-sectional study. A fourth control group consisted of 100 non-donors. In addition to measuring total protein, albumin and IgG levels, we determined parameters of humoral and cellular immunity, red cell and iron metabolism and recognized biochemical cardiovascular risk factors. RESULTS: The median annual net amount of plasma donated by the three donor groups was 37, 16 and 10 l, respectively (P < 0.0001). Donors had significantly lower total serum protein, albumin and IgG levels than non-donors (P < 0.0001), but the intensity of plasmapheresis had no influence on those parameters. Like non-donors, all plasma donors had normal humoral and cellular immunity. No increased rates of iron store depletion were observed in the three groups of plasma donors. Plasma donors were not at increased cardiovascular risk. CONCLUSIONS: Regular donor plasmapheresis of up to 45 l of plasma per year appears to be as safe as more moderate plasmapheresis programmes, with respect to the parameters analysed in this study. Individuals donating under these conditions did not develop impaired humoral and cellular immunity, iron store depletion, or increased cardiovascular risk with regard to established biochemical risk markers. Prospective studies are required to determine more exactly than in retrospective analyses the reasons why donors withdraw from plasmapheresis programmes.

Effectiveness of the glycoprotein IIb/IIIa antagonist abciximab during percutaneous coronary interventions (PCI) in clinical practice at a single high-volume center.

OBJECTIVE: Randomized controlled trials (RCTs) showed that the glycoprotein (GP) IIb/IIIa antagonist abciximab is able to reduce ischemic complications during percutaneous transluminal coronary interventions (PCIs). Its effectiveness in daily clinical practice in unselected patients remains to be determined. DESIGN, SETTING AND PATIENTS: From 7/1997 until 12/2000, 3310 PCIs were performed at the Heart Center Ludwigshafen. Out of them, 1076 (32.5%) patients were nonrandomly treated with a GP IIb/ IIa antagonist. Patients who were treated with abciximab were matched with patients not treated with abciximab. The matching procedure resulted in 590 pairs of patients. RESULTS: Patients treated with abciximab were more likely to have a history of former PCI (13.7% versus 8.8%, p=0.008) or coronary artery bypass surgery (19.2% versus 12.8%, p=0.003). There were no differences in concomitant diseases, left ventricular function, number of vessels diseased or target vessel. However, patients treated with abciximab had a higher rate of more complex stenosis (> or =B2; 94.4% versus 80.7%, p<0.001) and a longer x-ray exposition (median 486 s versus 422 s, p<0.001). Treatment with abciximab was associated with a significantly lower incidence of the combined endpoint of death, reinfarction or stroke during the hospital stay (2.4% versus 4.4%, p=0.039). This was confirmed after adjustment for confounding parameters (p=0.034). There was no increase in the rate of severe bleeding in the abciximab group (p=0.347). After one year the rates for the combined endpoint were 8.5% in the control group and 6.2% in the abciximab group (univariate analysis, p=0.134; multivariate analysis, p=0.143). CONCLUSION: Treatment with abciximab during PCI in daily clinical practice at a high volume center in patients with a high rate of acute coronary syndromes seems to be as effective as shown in RCTs.