scholarly journals SARS-CoV-2 Neutralization in Commercial Lots of Plasma-derived Immunoglobulin

2021 ◽  
Author(s):  
Andreas Volk ◽  
Caroline Covini-Souris ◽  
Denis Kuehnel ◽  
Christian de Mey ◽  
Juergen Roemisch ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Levels ◽  
Passive Immunization ◽  
Lead Times ◽  
Vaccination Programs ◽  
Neutralization Capacity ◽  
Humoral Immunodeficiency ◽  
Serological Status ◽  
Ivig Preparation ◽  
Donor Population

Introduction: Patients suffering from primary or secondary immunodeficiency face times of increased insecurity and discomfort in the light of the raging Covid-19 pandemic, not knowing if and to what extend their comorbidities impact a potential Covid-19 course of disease. Furthermore, recently available vaccination options might not be amenable or effective for all patients of this heterogeneous population. Therefore, these patients often rely on passive immunization with plasma-derived, intravenous or subcutaneous immunoglobulin (IVIG/SCIG). Whether the ongoing Covid-19 pandemic and/or the progress in vaccination programs lead to increased and potentially protective titers in plasma-derived immunoglobulins (Ig) indicated e.g. for humoral immunodeficiency remains a pressing question for this patient population. Purpose: Here we investigated SARS-CoV-2 reactivity of US plasma-derived IVIG/SCIG products from the end of 2020 until 06/2021 as well as in convalescent plasma (CP) from 05/2020 to 08/2020. Methods: Final containers of IVIG/SCIG and CP donations were analyzed by commercial ELISA for SARS-CoV-2 S1-RBD IgG as well as microneutralization assay using a patient-derived SARS-CoV-2 (D614G) isolate. Neutralization capacities of 313 plasma single donations and 119 plasma-derived IVIG/SCIG lots were determined. Results obtained from both analytical methods were normalized against the international WHO standard. Finally, based on dense pharmacokinetic profiles of an IVIG preparation from previously published investigations, possible steady-state plasma levels of SARS-CoV-2 neutralization capacities were approximated based on currently measured anti-SARS-CoV-2 potencies in IVIG/SCIG preparations. Results: CP donations presented with a high variability with regards to anti-SARS-reactivity in ELISA as well as in neutralization testing. While approximately 50% of convalescent donations were none/low neutralizing, approximately 10% were at or above 1000 IU/ml. IVIG/SCIG lots derived from pre-pandemic plasma donations did not show neutralizing capacities of SARS-CoV-2. Lots produced between 12/2020 and 06/2021, entailing plasma donations after emergence of SARS-CoV-2 showed a rapid and constant increase in anti-SARS-CoV-2 reactivity and neutralization capacity over time. Neutralization capacity increased from a mean of 20 IU/ml in 12/2020 to 505 IU/ml in 06/2021, while lot-to-lot variability was substantial. Pharmacokinetic (PK) extrapolations based on non-compartmental superposition principles using steady-state reference profiles from previously published PK investigations on IVIG in PID, yielded potential steady-state trough plasma levels of 16 IU/ml based on the average final container concentration from 05/2021 with 216 IU/ml. Maximum extrapolated trough levels could reach 64 IU/ml based on the latest maximal final container potency tested in 06/2021. Conclusions: SARS-CoV-2 reactivity and neutralization capacity in IVIG/SCIG produced from US plasma rapidly and in part exponentially increased in the first half of 2021. The observed increase of final container potencies is likely trailing the serological status of the US donor population in terms of Covid-19 convalescence and vaccination by at least 5 months due to production lead times and should in principle continue at least until fall 2021. In summary, the data support rapidly increasing levels of SARS-COV-2 antibodies in IVIG/SCIG products implicating that a certain level of protection could be possible against COVID-19 for regularly substituted PID/SID patients. Nevertheless, more research to confirm, which plasma levels are needed for protection against SARS-CoV-2 infection of immune-compromised patients is still needed.

Total and free steady-state plasma levels and pharmacokinetics of nifedipine in patients with terminal renal failure

1989 ◽  
Vol 37 (2) ◽  
pp. 185-189 ◽  
Author(s):  
L. v. Bortel ◽  
R. Böhm ◽  
J. Mooij ◽  
P. Schiffers ◽  
K. H. Rahn
Keyword(s):  
Renal Failure ◽  
Steady State ◽  
Plasma Levels ◽  
Terminal Renal Failure ◽  
State Plasma

Steady-State Plasma Levels and Pharmacokinetics of Guanfacine in Patients with Renal Insufficiency

Nephron ◽  
1989 ◽  
Vol 53 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Susan H. Carchman ◽  
Domenic A. Sica ◽  
Judith Davis ◽  
James T. Crowe Jr. ◽  
Albert J. Wasserman ◽  
...  
Keyword(s):  
Steady State ◽  
Renal Insufficiency ◽  
Plasma Levels ◽  
State Plasma

Repeated Ingestion of Grapefruit Juice Does Not Alter Clozapine's Steady-State Plasma Levels, Effectiveness, and Tolerability

2001 ◽  
Vol 62 (10) ◽  
pp. 812-817 ◽  
Author(s):  
Hsien-Yuan Lane ◽  
Michael W. Jann ◽  
Yue-Cune Chang ◽  
Chih-Chiang Chiu ◽  
Ming-Chyi Huang ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Levels ◽  
Grapefruit Juice ◽  
State Plasma

8-Hydroxylation and Glucuronidation of Mirtazapine in Japanese Psychiatric Patients: Significance of the Glucuronidation Pathway of 8-Hydroxy-Mirtazapine

2019 ◽  
Vol 52 (05) ◽  
pp. 237-244
Author(s):  
Masataka Shinozaki ◽  
Jason Pierce ◽  
Yuki Hayashi ◽  
Takashi Watanabe ◽  
Taro Sasaki ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Plasma Levels ◽  
High Performance ◽  
Psychiatric Patients ◽  
Plasma Concentrations ◽  
Steady State Concentration ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
State Concentration

Abstract Introduction  To investigate the metabolism of mirtazapine (MIR) in Japanese psychiatric patients, we determined the plasma levels of MIR, N-desmethylmirtazapine (DMIR), 8-hydroxy-mirtazapine (8-OH-MIR), mirtazapine glucuronide (MIR-G), and 8-hydroxy-mirtazapine glucuronide (8-OH-MIR-G). Methods  Seventy-nine Japanese psychiatric patients were treated with MIR for 1–8 weeks to achieve a steady-state concentration. Plasma levels of MIR, DMIR, and 8-OH-MIR were determined using high-performance liquid chromatography. Plasma concentrations of MIR-G and 8-OH-MIR-G were determined by total MIR and total 8-OH-MIR (i. e., concentrations after hydrolysis) minus unconjugated MIR and unconjugated 8-OH-MIR, respectively. Polymerase chain reaction was used to determine CYP2D6 genotypes. Results  Plasma levels of 8-OH-MIR were lower than those of MIR and DMIR (median 1.42 nmol/L vs. 92.71 nmol/L and 44.96 nmol/L, respectively). The plasma levels (median) of MIR-G and 8-OH-MIR-G were 75.00 nmol/L and 111.60 nmol/L, giving MIR-G/MIR and 8-OH-MIR-G/8-OH-MIR ratios of 0.92 and 59.50, respectively. Multiple regression analysis revealed that smoking was correlated with the plasma MIR concentration (dose- and body weight–corrected, p=0.040) and that age (years) was significantly correlated with the plasma DMIR concentration (dose- and body weight–corrected, p=0.018). The steady-state plasma concentrations of MIR and its metabolites were unaffected by the number of CYP2D6*5 and CYP2D6*10 alleles. Discussion  The plasma concentration of 8-OH-MIR was as low as 1.42 nmol/L, whereas 8-OH-MIR-G had an approximate 59.50 times higher concentration than 8-OH-MIR, suggesting a significant role for hydroxylation of MIR and its glucuronidation in the Japanese population.

Within-Individual Variation in Steady State Plasma Levels of Different Neuroleptics and Prolactin

1984 ◽  
Vol 144 (6) ◽  
pp. 625-629 ◽  
Author(s):  
R. G. McCreadie ◽  
Margaret Mackie ◽  
David H. Wiles ◽  
Aksel Jorgensen ◽  
Villy Hansen ◽  
...  
Keyword(s):  
Steady State ◽  
Individual Variation ◽  
Plasma Levels ◽  
State Level ◽  
Drug Analysis ◽  
Plasma Prolactin ◽  
Routes Of Administration ◽  
Chronic Schizophrenics ◽  
Before And After ◽  
State Plasma

SummaryEleven male chronic schizophrenics were given, serially, oral pimozide, fluphenazine, and flupenthixol; the two latter were also given intramuscularly as decanoates in oil. Oral haloperidol was given before and after each drug. Analysis of variance of steady state plasma levels of the different neuroleptics showed considerable within-individual variation in such levels, probably due to differences in absorption and metabolism and between routes of administration. The findings suggest that if a patient fails to respond to one neuroleptic, there may be good pharmacokinetic reasons for switching him to another belonging to a different group, or for giving the same neuroleptic by a different route of administration. The study also showed that previous administration of one neurololeptic may influence the steady state level of another. The various neuroleptics produced different effects on plasma prolactin levels.

Pharmacology and phase I/II study of continuous intravenous infusions of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme.

1988 ◽  
Vol 6 (5) ◽  
pp. 871-879 ◽  
Author(s):  
T J Kinsella ◽  
J Collins ◽  
J Rowland ◽  
R Klecker ◽  
D Wright ◽  
...  
Keyword(s):  
Steady State ◽  
Glioblastoma Multiforme ◽  
Phase I ◽  
Median Survival ◽  
Plasma Levels ◽  
Eastern Cooperative Oncology Group ◽  
Combined Modality Treatment ◽  
Wide Field ◽  
Outpatient Basis ◽  
Cox Regression Analysis

Forty-seven adult patients with glioblastoma multiforme (GBM) were treated in a phase I/II study combining continuous intravenous (IV) infusions of iododeoxyuridine (IdUrd) and hyperfractionated radiation therapy. IdUrd was administered as a continuous infusion (24 h/d) for two separate 14-day infusion periods. The dose of IdUrd was escalated from 500 to 1,200 mg/m2/d. The initial wide-field tumor volume was treated to 45 Gy at 1.5 Gy fractions twice daily over 3 weeks. Following a planned 2-week break, a reduced-field boost of 25 Gy was delivered using 1.25 Gy fractions twice daily over 2 weeks (total dose, 70 Gy over 9 weeks). The IdUrd infusion preceded both the wide-field and reduced-field irradiation by 1 week. All treatment was performed on an outpatient basis. Dose-limiting systemic toxicity to the bone marrow (primarily thrombocytopenia) and gastrointestinal (GI) tract (both stomatitis and diarrhea) established the maximum tolerable dose (MTD) at 1,000 mg/m2/d for a 14-day infusion. Significant local toxicity (within the radiation field) was not seen. The kinetics of IdUrd were linear with dose escalation and reached steady-state plasma concentrations of 1.3 to 3.4 mumol/L. The total body clearance of IdUrd was .82 L/min/m2. The primary metabolite, 5-iodouracil (IUra) approached steady state by day 6 of the infusion when plasma levels were 60 times higher than IdUrd. Plasma levels of uracil and thymine, but not thymidine, were elevated throughout the infusion. With a minimum follow-up of 1 year, ten patients remain alive, while 33 patients died of progressive disease, and four patients died of other causes (including one treatment-related death). The median survival for all 47 patient and for the 40 patients receiving the MTD was 45 and 47 weeks, respectively, with 12% and 14% survivals at 24 months. Using a Cox regression analysis, age (less than or equal to 50 years v greater than 50 years) and pretreatment performance status (PS) (Eastern Cooperative Oncology Group [ECOG]-PS 0 to 1 v PS 2 to 3) were independent, statistically significant (P2 less than .05) predictors of survival, with the ECOG status being a better predictor. Patients with a PS 0 to 1 (28 patients) had a median survival of 64 weeks with 21% survival at 24 months, compared with a median survival of 29 weeks and 0% survival at 12 months in the 19 patients with PS 2 to 3. The overall and subgroup survival data are at least comparable to other combined modality treatment approaches in patients with GBM.

A study of β-thromboglobulin and platelet factor-4 plasma levels in steady state sickle cell patients

1990 ◽  
Vol 61 (4) ◽  
pp. 245-247 ◽  
Author(s):  
S. Adamides ◽  
K. Konstantopoulos ◽  
M. Toumbis ◽  
D. Douratsos ◽  
A. Travlou ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell ◽  
Plasma Levels ◽  
Platelet Factor 4 ◽  
Platelet Factor

scholarly journals ADULT SICKLE CELL ANAEMIA PATIENTS IN BONE PAIN CRISIS HAVE ELEVATED PRO-INFLAMMATORY CYTOKINES

2018 ◽  
Vol 10 (1) ◽  
pp. e2018017 ◽  
Author(s):  
Adekunle Emmanuel Alagbe ◽  
John Ayodele Olaniyi ◽  
Oladapo Wale Aworanti
Keyword(s):  
Steady State ◽  
Sickle Cell ◽  
Plasma Levels ◽  
Bone Pain ◽  
Sickle Cell Anaemia ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Tnf Α ◽  
Pain Crisis ◽  
State Group

Background and Objective: Inflammatory markers that influence bone pain crisis (BPC) and other complications of sickle cell anaemia (SCA) are numerous and play various roles. This study determined the plasma levels of tumour necrosis factor (TNF) - α, interleukin - 8 (IL-8), and endothelin - 1 (ET-1) in adult SCA patients during BPC and in steady state. In addition, the plasma levels of these cytokines were correlated with the severity of BPC of the patients.Methods and Materials: Sixty adult SCA patients (30 during BPC and 30 during steady state) and 30 haemoglobin A controls were enrolled for this cross-sectional study. The severity of BPC was assessed clinically, and questionnaires were filled. Plasma levels of TNF- α, IL-8 and ET-1 were quantified by ELISA, and haematological parameters were determined using a 5-part auto-analyzer. Plasma levels were correlated with the severity of bone pain crisis. Results were considered statistically significant if p<0.05.Results: Plasma TNF-α, IL-8, and ET-1 were significantly elevated in the BPC group than in the steady state group and the controls. Plasma TNF-α, IL-8 and ET-1 were markedly higher in the severe BPC groups than the steady state and control groups, There was a positive correlation between TNF-α and ET-1 in the bone pain crisis group.Conclusion: Elevated levels of plasma TNF-α, IL-8, and ET-1 further establish the chronic inflammatory state in SCA and equally affirm their significant contribution, not only to pathogenesis but also to the severity of pain in SCA. Keywords: Sickle cell anaemia, Cytokines, Bone pain crisis, Severity, Steady state.

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