scholarly journals Rituximab and Canakinumab Use During Lactation: No Detectable Serum Levels in Breastfed Infants

Author(s):  
Nicole Bosshard ◽  
Astrid Zbinden ◽  
Klara Kristin Eriksson ◽  
Frauke Förger
2018 ◽  
Vol 35 (8) ◽  
pp. 1076-1080 ◽  
Author(s):  
Bryce Kayhart ◽  
Maria I. Lapid ◽  
Sarah Nelson ◽  
Julie L. Cunningham ◽  
Virginia H. Thompson ◽  
...  

In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.


2020 ◽  
pp. 40-50
Author(s):  
María Clara Álvarez Ferreira ◽  
Vanina Alejandra Alamino ◽  
Cristina del Valle Acosta ◽  
Laura Beatriz Onetti ◽  
Eduardo Daniel Musssano ◽  
...  

Introduction: Rheumatoid arthritis is characterized by synovium inflammation due to the infiltration of immune cells that secrete Th17 cytokines like IL-22 and IL-6. The dynamics of these cytokines during the treatment remain unknown. The aim of this study was to evaluate the levels of IL-22 and IL-6 serum and synovial fluid (SF) in correlation with different biochemical and clinical parameters and treatment-associated changes. Material and methods: Seventy-seven RA patients and 30 controls were recruited. Thirty patients were evaluated after 3 months of treatment and SF was collected of 12 patients. ESR, CRP, RF, anti-CCP hs, IL-22 e IL-6 were measured. DAS28 was used to assess disease activity and response to treatment followed EULAR criteria. Results: There were not differences in serum IL-22 and IL-6 levels between patients and controls. Cytokine levels decreased after treatment, mainly in responder patients. IL-22 was decreased and IL-6 was increased in SF compared to serum. IL-6 correlated positively with CRP and anti-CCPhs. ESR, CRP and DAS28 were increased in patients with detectable IL-6 compared to those with undetectable IL-6. Conclusion: In patients with detectable serum IL-22 and IL-6 levels before treatment initiation, follow-up of cytokine levels could be an useful additional tool to evaluate treatment response.


1985 ◽  
Vol 58 (2) ◽  
pp. 485-491 ◽  
Author(s):  
C. A. Hirshman ◽  
H. Downes

Antigen sensitization was induced in six Basenji-Greyhound (BG) dogs by weekly aerosol exposure to Ascaris suum. The effects on airway responsiveness to inhaled methacholine were studied before and at least 2 wk following Ascaris sensitization. All dogs developed detectable serum levels of Ascaris-specific immunoglobulin E (IgE), and five out of six dogs developed airway responsiveness to antigen over the 4- to 6-mo period. This was accompanied by a decrease rather than an increase in airway responsiveness to inhaled methacholine. When dogs were challenged with methacholine 30 min after Ascaris antigen aerosol challenge, however, dogs reactive to Ascaris became hyperresponsive to methacholine. The magnitude of the response to antigen correlated (r = 0.85) inversely with the dose of methacholine increasing pulmonary resistance 200%. These data show that in BG dogs airway responsiveness to methacholine is increased by acute antigen exposure but that sensitization of previously unsensitized dogs does not increase nonspecific airway responsiveness.


Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1340-1347
Author(s):  
J Cebon ◽  
P Dempsey ◽  
R Fox ◽  
G Kannourakis ◽  
E Bonnem ◽  
...  

A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.


2019 ◽  
Vol 104 (6) ◽  
pp. e8.2-e8
Author(s):  
T Maier ◽  
P Peirce ◽  
L Baird ◽  
SL Whitehouse ◽  
NKH Slater ◽  
...  

BackgroundAt an age when breastfeeding is the optimal nutritional support for infants, enteral drug delivery can be physically and emotionally challenging for parents. Delivery during breastfeeding could serve as an alternative to currently existing approaches. This study aimed to explore its feasibility and acceptability.MethodsVitamin B12 was administered as part of a single-centre feasibility study to breastfed infants at the University of Cambridge Addenbrooke´s Hospital NHS Trust. Hereby a solid formulation (tablet) was placed inside an ultra-thin silicone nipple shield, and worn by a mother during the feed. The study investigated i.) quantitative changes in B12 blood serum levels at baseline and 6–8 hours after the study feed, ii.) mothers’ expectations and experiences via a mixed method approach by a single investigator. Local ethics approval was obtained prior to any study procedures being undertaken (18/LO/0551).ResultsTwenty dyads completed the study protocol. In all cases, no residual tablet was left after the feed, and the tablet’s presence within the shield did not appear to impact feeding. A pharmacokinetic-dependent vitamin B12 increase to 1871 pg/mL (610–4981 pg/mL) from a baseline of 533 pg/mL (236–925 pg/mL) was observed. Mothers described the nipple shield´s surprising ease of use and comfort for delivery, not affecting normal breastfeeding behaviour/sensation, while decreasing infant/maternal distress compared to the use of an oral syringe. All mothers expressed their wish for this approach to become available to parents in the future. Reasoning included the desire (1) of parents to have choices in relation to their infants’ health, (2) to replace a medical intervention with one that was felt to be more ‘natural’.ConclusionsThis study showed that solid formulations can be used for therapeutic delivery whilst breastfeeding and is viewed by mothers as advantageous compared to currently available methods.Disclosure(s)FundingThe research was supported by a WD Armstrong PhD studentship for the Application of Engineering in Medicine, University of Cambridge, the German Academic Scholarship Foundation, and the Kurt Hahn Trust, University of Cambridge. Competing interests (applicable to all authors): None declared.


Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1340-1347 ◽  
Author(s):  
J Cebon ◽  
P Dempsey ◽  
R Fox ◽  
G Kannourakis ◽  
E Bonnem ◽  
...  

Abstract A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.


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