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openmit-licenseMay 2024View details →

Pharmacokinetic Relation Extraction Database (PRED)

Annotated data to perform Relation Extraction and extract pharmacokinetic (PK) parameter estimates from scientific text.  Training, development and test files are released in <a href="https://jsonlines.org/">JSONL format</a> and store the annoated data for training and evaluating end-to-end relation extraction models.  Each line in the JSONL files corresponds to an annotated sentence with the following information:  <ul> <li>text: Raw sentence</li> <li>relations: List or relations each containing:  <ul> <li>head_span : Head entity of the relation as a dictionary containing start character, end character and entity type label</li> <li>child_span: Child entity of the relation </li> <li>label: relation type label (i.e. either C_VAL, D_VAL or RELATED)</li> </ul> </li> <li>spans: List of entities mentioned in the sentence, specifying: (1) the character-level boundaries and (2) the entity type label of each annotation (i.e. either PK, VALUE, UNITS, RANGE or COMPARE). This field is not strictly required to train the model since all spans are defined within the relations.</li> <li>sentence_hash: Unique sentence ID</li> <li>metadata: Metadata with unique article, paragraph and sentence identifiers and the article section from which the sentence was extracted</li> </ul>

opencc-by-4.0Dec 2023View details →

Figure 3 in Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-β-D-(6"-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay

Figure 3. Photomicrography of exfoliated oral mucosa cells with: (A) karyorrhexis; (B) karyolysis; (C) micronucleus; (D) binucleation; and (E) macronucleus. Magnification X1000.

opencc-by-4.0Dec 2023View details →

Figure 2 in Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-β-D-(6"-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay

Figure 2. Cytotoxic effect of tiliroside (H. velutina) against RBC; (C-) Negative control (erythrocytes 0.5%), (C+) Positive control (1% Triton X-100). P <0.05 (*), P <0.01(**) and P <0.001 (***) versus positive control.

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Data from: In vitro to in vivo extrapolation from three-dimensional hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrythmia risk assessment

Proarrhythmic cardiotoxicity remains a substantial barrier to drug development as well as a major global health challenge. In vitro human pluripotent stem cell-based new approach methodologies have been increasingly proposed and employed as alternatives to existing in vitro and in vivo models that do not accurately recapitulate human cardiac electrophysiology or cardiotoxicity risk. In this study, we expanded the capacity of our previously established three-dimensional human cardiac microtissue model to perform quantitative risk assessment by combining it with a physiologically based pharmacokinetic model, allowing a direct comparison of potentially harmful concentrations predicted in vitro to in vivo therapeutic levels. This approach enabled the measurement of concentration responses and margins of exposure for two physiologically relevant metrics of proarrhythmic risk (i.e., action potential duration and triangulation assessed by optical mapping) across concentrations spanning three orders of magnitude. The combination of both metrics enabled accurate proarrhythmic risk assessment of four compounds with a range of known proarrhythmic risk profiles (i.e., quinidine, cisapride, ranolazine, and verapamil) and demonstrated close agreement with their known clinical effects. Action potential triangulation was found to be a more sensitive metric for predicting proarrhythmic risk associated with the primary mechanism of concern for pharmaceutical-induced fatal ventricular arrhythmias, delayed cardiac repolarization due to inhibition of the rapid delayed rectifier potassium channel, or hERG channel. This study advances human induced pluripotent stem cell-based three-dimensional cardiac tissue models as new approach methodologies that enable in vitro proarrhythmic risk assessment with high precision of quantitative metrics for understanding clinically relevant cardiotoxicity.

opencc-zeroJun 2024View details →

The Brain and Propranolol Pharmacokinetics in the Elderly-Figure 1.(a)Results of the Monte-Carlo simulations to describe pharmacokinetics of young patients with validation from the Taegtmeyer 2014 publication(Taegtmeyer et al., 2014)

Propranolol has been found to be therapeutically effective, to obtain a clinical response by beta-adrenoceptor blockade, at plasma levels of greater than 20 ng/mL(Coltart et al., 1971; Frishman, 1988; Johnsson and Regàrdh, 1976). Thus, to display the data, we used highlighted plasma concentration where the pharmacokinetic curve falls below 20ng/mL threshold for therapeutic efficacy in the patient’s plasma.

Figure 2.(a)Results of the Monte-Carlo simulations describing a population of elderly patients after a single oral dose of propranolol.-The Brain and Propranolol Pharmacokinetics in the Elderly

In effort to identify the recommended Propranolol dosage for elderly patients, we identified the patient package inserts from the Food and Drug Administration (FDA) Inderal label, who manufacture propranolol. Based from FDA Wyeth Propranolol label, for dosing in the geriatric population,the label states that there were not sufficient numbers of clinical study participants who were 65-years and older to properly determine the difference in response young and elderly patients.

Figure 6.Amygdala hypofunction after a single oral 40-mg dose, 1.5-hours post-dose, in young study participants.The image has been adapted from (Hurlemann et al., 2010).-The Brain and Propranolol Pharmacokinetics in the Elderly

In the past decade, there has been much interest in identifying treatment in adding to the current treatment options for war veterans suffering from Post-Traumatic Stress Disorder (PTSD). The studies investigating secondary-preventative measures for PTSD using Propranolol due to the drug’s ability to inhibit the actions of the neurotransmitter norepinephrine,which has been implicated to enhance the consolidation(McGhee et al., 2009; Pitman et al., 2002; Stein et al., 2007).Further, in a double-blind, placebo-controlled,functional Magnetic Resonance Imaging (fMRI) study, in healthy volunteers, Hurlemann et al. found that a single oral 40mg dose of propranolol attenuatedthe leftbasolateral amygdala responses to the face perception paradigm(Hurlemann et al., 2010). The study participants were eighteen healthy (9 females, 9 males; mean age 23 years; age range 19–31 years) who had their fMRI acquisition 1.5-hours after the oral administration of propranolol. An adapted image of the study findings are shown in Figure 6.

Figure 5.(a)Linear (y=0.45x + 57.74) dose-response relationship between plasma propranolol to % β- adrenergeric blockade derived from healthy study participants and translate into patients with angina pectoris. This image has been adapted from(Pine et al., 1975).-The Brain and Propranolol Pharmacokinetics in the Elderly

Apharmacodynamic model,with parameters in the table below, may be used to visualize the propranolol concentration-effect (β-blockade) relationship in patients suffering from angina pectoris. These results have been adapted from the Pine et al article published in Circulation in 1975 which identified a linear relationship plasma Propranolol (ng/mL) to an effect of % β-Adrenergic Blockade in a single-oral dose of 40mg Propranolol in exercising individuals (Pine et al., 1975).

opencc-by-4.0Jan 2018View details →

Figure 4. Simulation (Monte-Carlo, n=200) results elderly patients taking a 10mg oral dose resulting in similar Cmax, maximum plasma concentration, to the young patients taking a 40mg oral dose. The dotted lines illustrate the 10th and 90th percentiles of plasma levels of the elderly population with a 10mg oral administration of propranolol.-The Brain and Propranolol Pharmacokinetics in the Elderly

Thus, the package insert (see 1) recommends clinicians start at the lower end of the dosing range, without further details. Similarly, Pfizer manufactures Inderal® LA (Propranolol HCI), which is the long-acting form of propranolol and their package insert (see 2) states, “There is no information available for elderly patients.” Though the kinetics for the long-acting formdiffers from the standard form, manufactured by Wyeth, we would suspect a 10mg dose for the elderly would achieve a similar maximum plasma concentration (Cmax) to that of the younger patient cohort.This 10mg, which is 25% of the original 40mg, dosing schedule is based on our simulations at 10mg in the geriatric population.

Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

ClinicalTrials.gov study NCT03660839. IPD Sharing: YES. Countries: 5. Publications: 1.

Safety, Pharmacokinetics and Efficacy of Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes

ClinicalTrials.gov study NCT03005288. IPD Sharing: YES. Countries: 2. Publications: 1.

Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval and Pharmacokinetics in HER2-Expressing Breast Cancer

ClinicalTrials.gov study NCT03366428. IPD Sharing: YES. Countries: 1. Publications: 1.

Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric PIDD Subjects

ClinicalTrials.gov study NCT03277313. IPD Sharing: YES. Countries: 1. Publications: 0.

To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

ClinicalTrials.gov study NCT02497612. IPD Sharing: YES. Countries: 7. Publications: 1.

Safety and Pharmacokinetics of IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)

ClinicalTrials.gov study NCT04137224. IPD Sharing: YES. Countries: 5. Publications: 1.

A Study to Assess the Relative Bioavailability, Effect of Food, and Gastric Potential Hydrogen (pH) Modification on the Pharmacokinetics (PK) of TAK-931 in Participants With Advanced Solid Tumors

ClinicalTrials.gov study NCT03708211. IPD Sharing: YES. Countries: 1. Publications: 1.

Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

ClinicalTrials.gov study NCT01410890. IPD Sharing: YES. Countries: 6. Publications: 1.

Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

ClinicalTrials.gov study NCT02004691. IPD Sharing: YES. Countries: 17. Publications: 1.

Safety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation

ClinicalTrials.gov study NCT04294459. IPD Sharing: YES. Countries: 2. Publications: 2.