Pharmacokinetics Of Intravenous Immunoglobulin Research Articles

Updates in the management of Guillain Barre Syndrome

Barré and Strohl in 1916. Although GBS has a good prognosis (5% mortality rate), about 10% of patients experience serious disability one year after the start of neurological onset. Recent research of GBS shows that the process involves a number of subtypes with different immunological mechanism and a spectrum of clinical syndrome of acute inflammatory neuropathy. Antibodies against peripheral nerve gangliosides and their own complements are recognized as an important mechanism of nerve damage in GBS. Pharmacokinetics of intravenous immunoglobulin (IVIg) therapy and other related factors that influence prognosis has been researched. In order to investigate the possible role of complement inhibition in GBS management, new studies will be conducted. The management of GBS should be provided in appropriate hospital units, with specialist teams, intensive care and rehabilitation facilities as essential parts. This article aims to provide updated management of GBS.Citation: Imelda NC, Baktir F, Fidiana, Hidayati HB, Basuki M. Updates in the management of Guillain Barre Syndrome. Anaesth Pain & Intensive Care 2018;22 Suppl 1:S54-S57

Neonatal Fc receptor promoter gene polymorphism does not predict pharmacokinetics of IVIg or the clinical course of GBS.

Treatment of Guillain‐Barré syndrome with a standard course of high‐dose intravenous immunoglobulin (IVIg) results in a variable clinical recovery which is associated with changes in serum IgG levels after treatment. The neonatal Fc‐receptor protects IgG from degradation, and a genetic polymorphism in its promoter region that influences the expression of Fc‐receptor, may in part explain the variation in IgG levels and outcome. This polymorphism was determined by polymerase chain reaction in a cohort of 257 patients with Guillain‐Barré syndrome treated with IVIg. We could not demonstrate a relation between this polymorphism, the pharmacokinetics of IVIg, or the clinical course and outcome.

A two-center study on the pharmacokinetics of intravenous immunoglobulin before and during pregnancy in healthy women with poor obstetrical histories

Despite the increasing use of intravenous immunoglobulin (IVIG) in obstetrics, information on its pharmacokinetics and optimal dosing during each trimester pregnancy is lacking. The aim of this study was to characterize IVIG pharmacokinetics in pregnant women with a history of idiopathic secondary recurrent miscarriage or obstetrical antiphospholipid syndrome and to make dosing recommendations by comparing serum immunoglobulin G (IgG) concentrations in women receiving IVIG to placebo controls, before and during pregnancy. Women enrolled in an IVIG trial for idiopathic secondary recurrent miscarriage (n = 25) or an IVIG study for obstetrical antiphospholipid syndrome (n = 10); 22 received IVIG 0.5-1.0 g/kg and 13 received the equivalent volume of saline, every 4 weeks from pre-pregnancy until 18-20 weeks of gestation, with dosing adjusted for her weight prior to each infusion. Serum IgG concentrations were measured by rate nephelometry before and 0.5 h, and 1, 2, 3 and 4 weeks following an infusion. Sampling was performed pre-pregnancy and in the first and second trimesters. Area under the curve (AUC) did not differ significantly within the IVIG group between the three sampling periods. Estimated contributions of IVIG [calculated as mean AUC (IVIG group) minus mean AUC (control group)] were 4890.8 g h/l pre-pregnancy, 5591.4 g h/l first trimester and 4755.1 g h/l second trimester (P> 0.05, non-significant). For the IVIG 0.5 and 1.0 g/kg subgroups, the overall estimated contribution of exogenous IVIG was ~4000 and ~6400 g h/l, respectively. With a weight-adjusted dosage of IVIG, drug exposure, based on AUC calculations, was maintained at the pre-pregnancy level. Therefore, we recommend a weight-adjusted dosage of IVIG during the first and second trimesters.

Serum IgG levels as biomarkers for optimizing IVIg therapy in CIDP

Intravenous immunoglobulin (IVIg) is a proven effective treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS). In GBS, patients show a large variability in serum immunoglobulin G (IgG) levels after standard IVIg treatment and a large increase in serum IgG levels (ΔIgG) was associated with a better outcome. Whether this is also the case in CIDP is not known. In contrast to GBS, most patients with CIDP need regular IVIg treatment for a prolonged period of time but the speed and magnitude of clinical response varies considerably between patients. Some patients with CIDP may need at least two IVIg courses before clinical signs of improvement become clear. At present, this clinical response is the only indicator used to adjust the IVIg dose and interval during maintenance treatment. Biomarkers reflecting disease activity or IVIg pharmacokinetics might be helpful to monitor patients and find the optimal dosage and frequency of IVIg treatment for individual patients. A recent prospective study in CIDP indicated that the increased ΔIgG after standard IVIg dosage during maintenance treatment was relatively constant within individual patients, but differed considerably between patients who were treated with the same stable dosage and interval of IVIg. Further studies are required to determine whether this variation in pharmacokinetics of IVIg is related with clinical recovery and whether IgG levels can be used as biomarkers to monitor and to adjust the optimal IVIg dosage in individual patients with CIDP.

Pharmacokinetics of Intravenous Immunoglobulin and Outcome of Guillain-Barre Syndrome

The relation of pharmacokinetics of intravenous immunoglobulin (IVIg) to the outcome of Guillain-Barre syndrome (GBS) was determined in 174 adults treated at Erasmus Medical Center, Rotterdam, The Netherlands.

Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain‐Barré syndrome

Intravenous immunoglobulin (IVIg) is the first choice treatment for Guillain-Barré syndrome (GBS). All patients initially receive the same arbitrary dose of 2g per kg body weight. Not all patients, however, show a good recovery after this standard dose. IVIg clearance may depend on disease severity and vary between individuals, implying that this dose is suboptimal for some patients. In this study, we determined whether the pharmacokinetics of IVIg is related to outcome in GBS. We included 174 GBS patients who had previously participated in 2 randomized clinical trials. At entry, all patients were unable to walk unaided and received a standard dose of IVIg. Total IgG levels in serum samples obtained immediately before and 2 weeks after the start of IVIg administration were determined by turbidimetry and related to clinical outcome at 6 months. The increase in serum IgG (DeltaIgG) 2 weeks after IVIg treatment varied considerably between patients (mean, 7.8g/L; standard deviation, 5.6g/L). Patients with a low DeltaIgG recovered significantly more slowly, and fewer reached the ability to walk unaided at 6 months (log-rank p < 0.001). In multivariate analysis adjusted for other known prognostic factors, a low DeltaIgG was independently associated with poor outcome (p = 0.022). After a standard dose of IVIg treatment, GBS patients show a large variation in pharmacokinetics, which is related to clinical outcome. This may indicate that patients with a small increase in serum IgG level may benefit from a higher dosage or second course of IVIg.

Pharmacokinetics of intravenous immunoglobulin administered via subcutaneous route in patients with hypogamma-globulinemia

Pharmacokinetics of intravenous immunoglobulin administered via subcutaneous route in patients with hypogamma-globulinemia

Pharmacokinetics of intravenous immunoglobulin in very low birth weight neonates

We studied the pharmacokinetics of single doses of intravenous immunoglobulin (IVIG) of 1000, 750 and 500 mg/kg administered to 21 neonates with birth weights from 750 to 1500 g. No adverse effects were detected. Mean pharmacokinetic values for the large, intermediate and small dose groups, respectively, were: elimination half-life, 19.6, 28.7 and 22.1 days; clearance, 5.2, 5.6 and 3.7 ml/kg/day; volume of distribution, 151, 255 and 130 ml/kg. Mean peak IgG concentrations in serum were 1826, 1476 and 1257 mg/dl for the large, intermediate and small dose groups, respectively. Mean IgG on post-infusion Days 1 to 28 were similar for the intermediate and small dose groups but were higher in the larger dose group. Both large and intermediate doses achieved larger increases in IgG over preinfusion values (delta IgG) than the small dose. The differences in delta IgG between the large and intermediate doses were less notable. The wide variability observed indicates that individualization of intravenous immunoglobulin dosage will be required in these patients.