Search

Background and Objectives Pharmacokinetics, safety and tolerability of escalating infusion rates of BT090, a 10% intravenous immunoglobulin ( IVIg), were studied in patients with primary immunodeficiency disease. Materials and Methods In Part A, patients ( n = 30) received 3 infusions of BT090 at their pretrial dose and dosing interval; the infusion rate of BT090 was increased from 0·3 to 1·4 to 2·0 ml/kg/h for each infusion in each patient initially at 30-min intervals. Pharmacokinetics was evaluated at the 3rd infusion ( n = 24). At the 4th infusion, infusion rates were to be gradually escalated from 0·3 to 1·4 to 4·0 to a maximum of 8·0 ml/kg/h initially at 30-min intervals to establish the maximum tolerated infusion rate per patient. Results The pharmacokinetic characteristics and safety profile of BT090 were comparable with those of other IVIgs, including Intratect®. Escalation of infusion rates was well tolerated, allowing identification of individual patient's maximum tolerated infusion rate. At subsequent infusions, all patients tolerated their individually defined maximum infusion rate: 17 patients (68·0%) tolerated infusion rates of 6·0 or 8·0 ml/kg/h and four patients (16%) had maximum tolerated infusion rates of <4·0 ml/kg/h at subsequent infusions. Escalation of infusion rates shortened infusion time from a median of around 2·5 h to around 1·6 h. SAEs were reported in three patients, but none was related to BT090 treatment. Conclusions Shortening infusion time may reduce overall healthcare spending, for example nursing time needed, and also minimize disruption of patients' daily routine, especially for those patients in work or school settings. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T) is an early onset autosomal recessive ataxia associated with characteristic chromosomal aberrations, cell cycle checkpoint defects, cancer susceptibility, and sensitivity to ionizing radiation. We utilized the protein truncation test (PTT), and single strand conformation polymorphism (SSCP) on cDNA, as well as denaturing high performance liquid chromatography (dHPLC) on genomic DNA (gDNA) to screen for mutations in 24 Polish A-T families. Twenty-six distinct Short Tandem Repeat (STR) haplotypes were identified. Three founder mutations accounted for 58% of the alleles. Three-quarters of the families had at least one recurring (shared) mutation, which was somewhat surprising given the low frequency of consanguinity in Poland. STR haplotyping greatly improved the efficiency of mutation detection. We identified 44 of the expected 48 mutations (92%): sixty-nine percent were nonsense mutations, 23% caused aberrant splicing, and 5% were missense mutations. Four mutations have not been previously described. Two of the Polish mutations have been observed previously in Amish and Mennonite A-T patients; this is compatible with historical records. Shared mutations shared the same Single Nucleotide Polymorphism (SNP) and STR haplotypes, indicating common ancestries. The Mennonite mutation, 5932 G>T, is common in Russian A-T families, and the STR haplovariants are the same in both Poland and Russia. Attempts to correlate phenotypes with genotypes were inconclusive due to the limited numbers of patients with identical mutations. [ABSTRACT FROM AUTHOR]

Background and Objectives Careful evaluation of the pharmacokinetic properties of a new immunoglobulin G (IgG) preparation is necessary to ensure that the product will not deviate significantly from existing products, in terms of pharmacological activity. Materials and Methods A prospective, open and uncontrolled trial was performed in 16 patients with primary immunodeficiency syndromes. Patients who had been under replacement therapy with licensed preparations prior to study inclusion, received 280 ± 60 mg/kg of a solution of IgG, ready for intravenous administration, every 3 weeks for 6 months. Trough and peak plasma levels were measured immediately before and 1 h after each infusion, respectively. Pharmacokinetic parameters were calculated for total IgG and IgG subclasses. Results Total IgG, IgG1, IgG2 and IgG3 declined mono-exponentially in contrast to IgG4 which showed a bi-exponential decline. Half-lives which were highly variable among patients were similar for total IgG, IgG1 and IgG2 (35.9 10.8, 36.3 9.2, and 37.1 13.9 days, respectively) and shorter for IgG3 and IgG4 (28.6 10.4 and 15.6 4.5 days, respectively). Conclusions The decline of IgG4 probably reflected a complex catabolic pathway specific for this subclass. As the plasma level of IgG4 is low, the decline of total IgG remained unaffected. Pharmacokinetic properties were consistent with results reported elsewhere in patients undergoing replacement therapy for primary immunodeficiency syndromes. [ABSTRACT FROM AUTHOR]