A multiscale absorption and transit model for oral delivery of hydroxychloroquine: Pharmacokinetic modeling and intestinal concentration prediction to assess toxicity and drug‐induced damage in healthy subjects

2020 ◽  
Vol 36 (12) ◽  
Author(s):  
Ravishekar Kannan ◽  
Andrzej Przekwas
Keyword(s):  
Oral Delivery ◽  
Healthy Subjects ◽  
Pharmacokinetic Modeling ◽  
Drug Induced ◽  
Transit Model ◽  
Concentration Prediction

Peripheral Autonomic Potentials in Primary Headache and Drug-Induced Headache

Cephalalgia ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 216-221 ◽  
Author(s):  
S Evers ◽  
H Voss ◽  
B Bauer ◽  
P Sörös ◽  
I-W Husstedt
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Drug Abuse ◽  
Healthy Subjects ◽  
Primary Headache ◽  
Tension Type Headache ◽  
Low Back ◽  
Drug Induced ◽  
Type Headache ◽  
Drug Induced Headache

Autonomic functions of different primary headache types have been investigated in several studies, most of them analyzing cardiovascular reflex mechanisms or biochemical changes. The results are contradictory; only in tension-type headache and in cluster headache has a sympathetic hypofunction been shown in a preponderance of studies. We analyzed the peripheral autonomous potentials (PAPs) in different primary headache types and in drug-induced headache and compared the results with those of healthy subjects and of patients with low back pain. Latencies of PAPs were significantly increased in all headache types but not in low back pain; amplitudes of PAPs did not show significant differences compared to healthy subjects. Patients with a long duration of drug abuse had increased PAP latencies, whereas patients with a high number of migraine attacks per year had decreased latencies. Our data suggest that sympathetic hypo-function as measured by PAP latencies is a general phenomenon in headache but not in all pain syndromes. Drug abuse leads to an increase of this hypofunction. While measuring PAPs is not an appropriate method by which to differentiate between headache disorders, it allows assessment of autonomic disturbances in primary and drug-induced headache.

Seroprevalence of PF4/Heparin Antibodies among Blood Bank Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4536-4536
Author(s):  
Poulomi J. Pai ◽  
Julianna E McCracken ◽  
Gowthami M Arepally
Keyword(s):  
Healthy Subjects ◽  
Blood Donation ◽  
Blood Bank ◽  
Blood Type ◽  
Autoimmune Response ◽  
Healthy Population ◽  
Drug Induced ◽  
Immune Disorder ◽  
Platelet Factor ◽  
Naturally Occurring

Abstract Heparin-Induced Thrombocytopenia (HIT) is classically viewed as a drug-induced immune disorder triggered by exposure to the anticoagulant drug, heparin. However, HIT may also be considered a dysregulated autoimmune response to two naturally occurring substances, Platelet Factor 4 (PF4), a platelet protein, and heparin, a tissuederived glycosaminoglycan. Until recently, studies of HIT and PF4/heparin antibody seroconversion have been exclusively focused on patients exposed to heparin or heparinlike drugs, including low-molecular weight heparin, the heparinoids and the synthetic agent, fondaparinux. Recent reports, however, indicate that PF4/heparin antibodies may arise spontaneously in some individuals in the absence of heparin (Warkentin Am J Med 2008; Hursting J Thromb Thrombolysis, 2008). We undertook this study to document the seroprevalance of “naturally-occurring” PF4/heparin antibodies in healthy subjects without prior heparin exposure. To study “healthy” subjects, we used blood bank donors as a surrogate population. Samples from blood bank units were obtained through Duke Transfusion services/American Red Cross (ARC). Donors met eligibility criteria for blood donation to the ARC and generally, represent a healthy population (http://www.redcross.org/services/biomed/0,1082,0_557_,00.html#hem). A Duke IRB waiver was issued due to use of anonymous samples. Plasma from donor units/segments were assayed in duplicate for the presence of PF4/heparin antibodies using a commercially available PF4/heparin ELISA (PF4 enhanced IgG,A,M kits, Genetics Technology Institute, Waukesha, WY). Positivity was defined by the manufacturer as A405nm ≥0.4. Positive samples were stratified into low, (A405nm=0.4–0.6), intermediate (A405nm=0.61–0.99) or high-positive values (A405nm≥1.0). High and intermediate positive samples were further isotyped using IgG and IgM specific antibodies (Sigma, St. Louis, MO). Of the 970 blood bank donors tested to date, 31 samples (3.2%) were positive using the manufacturer’s cut-off value. Repeat testing confirmed positivity in all 31 samples. Of those testing positive, 26 were low-positive (2.3% of overall cohort; 84% of all positive samples), 1 sample was intermediate positive (0.1% of overall cohort; 3.2% of positive samples) and 5 samples were high-positive (0.5% overall cohort; 16% of positive samples). Isotyping of 6 high/intermediate positive samples revealed IgG in 3 patients, IgM in the remainder. There was no correlation between antibody positivity and ABO blood type. In summary, our data reveals a high prevalence of PF4/heparin antibodies, the majority of which are low-positive values (~84%). Many of these low-positive samples likely reflect background “noise” of the assay and could be eliminated using a higher cut-off for positivity. We also found a seroprevalance of 0.5% of high positive antibodies, of IgG and IgM isotype, supporting the notion that some individuals may have “naturally-occuring”

scholarly journals Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

2017 ◽  
Vol 8 (2) ◽  
pp. 226-234 ◽  
Author(s):  
Tadahiro Shinozawa ◽  
Koki Nakamura ◽  
Masanobu Shoji ◽  
Maya Morita ◽  
Maya Kimura ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Qt Prolongation ◽  
Drug Induced ◽  
Individual Susceptibility
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