LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 97

Search options

  1. Article ; Online: Physiologically Based Modeling to Predict Monoclonal Antibody Pharmacokinetics in Humans from in vitro Physiochemical Properties.

    Hu, Shihao / Datta-Mannan, Amita / D'Argenio, David Z

    mAbs

    2022  Volume 14, Issue 1, Page(s) 2056944

    Abstract: A model-based framework is presented to predict monoclonal antibody (mAb) pharmacokinetics (PK) in humans based ... ...

    Abstract A model-based framework is presented to predict monoclonal antibody (mAb) pharmacokinetics (PK) in humans based on
    MeSH term(s) Antibodies, Monoclonal/pharmacokinetics ; Heparin ; Humans ; Kinetics ; Models, Biological ; Tissue Distribution
    Chemical Substances Antibodies, Monoclonal ; Heparin (9005-49-6)
    Language English
    Publishing date 2022-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2537838-7
    ISSN 1942-0870 ; 1942-0870
    ISSN (online) 1942-0870
    ISSN 1942-0870
    DOI 10.1080/19420862.2022.2056944
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Analysis of Complex Absorption After Multiple Dosing: Application to the Interaction Between the P-glycoprotein Substrate Talinolol and Rifampicin.

    Weiss, Michael / D'Argenio, David Z / Siegmund, Werner

    Pharmaceutical research

    2022  Volume 39, Issue 12, Page(s) 3293–3300

    Abstract: Purpose: In order to clarify the effect of rifampicin on the bioavailability of the P-glycoprotein substrate talinolol, its absorption kinetics was modeled after multiple-dose oral administration of talinolol in healthy subjects.: Methods: A sum of ... ...

    Abstract Purpose: In order to clarify the effect of rifampicin on the bioavailability of the P-glycoprotein substrate talinolol, its absorption kinetics was modeled after multiple-dose oral administration of talinolol in healthy subjects.
    Methods: A sum of two inverse Gaussian functions was used to calculate the time course of the input rate into the systemic circulation.
    Results: The estimated rate of drug entry into the systemic circulation revealed two distinct peaks at 1 and 3.5 h after administration. Rifampicin did not affect bioavailability of talinolol, but did shift the second peak of the input function by 1.3 h to later times. Elimination clearance and one of the intercompartmental distribution clearances increased significantly under rifampicin treatment.
    Conclusions: Rifampicin changes the time course of absorption rate but not the fraction absorbed of talinolol. The model suggests the existence of two intestinal absorption windows for talinolol.
    MeSH term(s) Humans ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Rifampin ; Adrenergic beta-Antagonists ; ATP Binding Cassette Transporter, Subfamily B ; Propanolamines
    Chemical Substances ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Rifampin (VJT6J7R4TR) ; talinolol (3S82268BKG) ; Adrenergic beta-Antagonists ; ATP Binding Cassette Transporter, Subfamily B ; Propanolamines
    Language English
    Publishing date 2022-09-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 843063-9
    ISSN 1573-904X ; 0724-8741 ; 0739-0742
    ISSN (online) 1573-904X
    ISSN 0724-8741 ; 0739-0742
    DOI 10.1007/s11095-022-03397-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Monoclonal Antibody Pharmacokinetics in Cynomolgus Monkeys Following Subcutaneous Administration: Physiologically Based Model Predictions from Physiochemical Properties.

    Hu, Shihao / Datta-Mannan, Amita / D'Argenio, David Z

    The AAPS journal

    2022  Volume 25, Issue 1, Page(s) 5

    Abstract: An integrated physiologically based modeling framework is presented for predicting pharmacokinetics and bioavailability of subcutaneously administered monoclonal antibodies in cynomolgus monkeys, based on in silico structure-derived metrics ... ...

    Abstract An integrated physiologically based modeling framework is presented for predicting pharmacokinetics and bioavailability of subcutaneously administered monoclonal antibodies in cynomolgus monkeys, based on in silico structure-derived metrics characterizing antibody size, overall charge, local charge, and hydrophobicity. The model accounts for antibody-specific differences in pinocytosis, transcapillary transport, local lymphatic uptake, and pre-systemic degradation at the subcutaneous injection site and reliably predicts the pharmacokinetics of five different wild-type mAbs and their Fc variants following intravenous and subcutaneous administration. Significant associations were found between subcutaneous injection site degradation rate and the antibody's local positive charge of its complementarity-determining region (R = 0.56, p = 0.0012), antibody pinocytosis rate and its overall positive charge (R = 0.59, p = 0.00063), and antibody paracellular transport and its overall charge together with hydrophobicity (R = 0.63, p = 0.00096). Based on these results, population simulations were performed to predict the relationship between bioavailability and antibody local positive charge. In addition, model simulations were conducted to calculate the relative contribution of absorption pathways (lymphatic and blood), pre-systemic degradation pathways (interstitial and lysosomal), and the influence of injection site lymph flow on antibody bioavailability and pharmacokinetics. The proposed physiologically based modeling framework integrates fundamental mechanisms governing antibody subcutaneous absorption and disposition, with structured-based physiochemical properties, to predict antibody bioavailability and pharmacokinetics in vivo.
    MeSH term(s) Animals ; Macaca fascicularis ; Antibodies, Monoclonal ; Biological Availability ; Immunotherapy ; Injections, Subcutaneous
    Chemical Substances Antibodies, Monoclonal
    Language English
    Publishing date 2022-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1550-7416
    ISSN (online) 1550-7416
    DOI 10.1208/s12248-022-00772-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Book ; Conference proceedings: The emerging scientific discipline of pharmacometrics

    Pfister, Marc / D'Argenio, David Z.

    [includes work presented at the first two meetings of the American Conference on Pharmacometrics in Tucson, Arizona (2008), and Mystic, Connecticut (2009)]

    (The journal of clinical pharmacology ; 50, Suppl. 1)

    2010  

    Event/congress American Conference on Pharmacometrics (1, 2008, TucsonAriz.) ; American Conference on Pharmacometrics (2, 2009, MysticConn.)
    Author's details guest ed.: Marc Pfister and David Z. D'Argenio
    Series title The journal of clinical pharmacology ; 50, Suppl. 1
    Collection
    Language English
    Size 158S S. : Ill., graph. Darst.
    Publisher Sage
    Publishing place Thousand Oaks, CA
    Publishing country United States
    Document type Book ; Conference proceedings
    HBZ-ID HT016526066
    Database Catalogue ZB MED Medicine, Health

    Kategorien

  5. Article ; Online: Long-term forecasting of a motor outcome following rehabilitation in chronic stroke via a hierarchical bayesian dynamic model.

    Schweighofer, Nicolas / Ye, Dongze / Luo, Haipeng / D'Argenio, David Z / Winstein, Carolee

    Journal of neuroengineering and rehabilitation

    2023  Volume 20, Issue 1, Page(s) 83

    Abstract: Background: Given the heterogeneity of stroke, it is important to determine the best course of motor therapy for each patient, i.e., to personalize rehabilitation based on predictions of long-term outcomes. Here, we propose a hierarchical Bayesian ... ...

    Abstract Background: Given the heterogeneity of stroke, it is important to determine the best course of motor therapy for each patient, i.e., to personalize rehabilitation based on predictions of long-term outcomes. Here, we propose a hierarchical Bayesian dynamic (i.e., state-space) model (HBDM) to forecast long-term changes in a motor outcome due to rehabilitation in the chronic phase post-stroke.
    Methods: The model incorporates the effects of clinician-supervised training, self-training, and forgetting. In addition, to improve forecasting early in rehabilitation, when data are sparse or unavailable, we use the Bayesian hierarchical modeling technique to incorporate prior information from similar patients. We use HBDM to re-analyze the Motor Activity Log (MAL) data of participants with chronic stroke included in two clinical trials: (1) the DOSE trial, in which participants were assigned to a 0, 15, 30, or 60-h dose condition (data of 40 participants analyzed), and (2) the EXCITE trial, in which participants were assigned a 60-h dose, in either an immediate or a delayed condition (95 participants analyzed).
    Results: For both datasets, HBDM accounts well for individual dynamics in the MAL during and outside of training: mean RMSE = 0.28 for all 40 DOSE participants (participant-level RMSE 0.26 ± 0.19-95% CI) and mean RMSE = 0.325 for all 95 EXCITE participants (participant-level RMSE 0.32 ± 0.31), which are small compared to the 0-5 range of the MAL. Bayesian leave-one-out cross-validation shows that the model has better predictive accuracy than static regression models and simpler dynamic models that do not account for the effect of supervised training, self-training, or forgetting. We then showcase model's ability to forecast the MAL of "new" participants up to 8 months ahead. The mean RMSE at 6 months post-training was 1.36 using only the baseline MAL and then decreased to 0.91, 0.79, and 0.69 (respectively) with the MAL following the 1st, 2nd, and 3rd bouts of training. In addition, hierarchical modeling improves prediction for a patient early in training. Finally, we verify that this model, despite its simplicity, can reproduce previous findings of the DOSE trial on the efficiency, efficacy, and retention of motor therapy.
    Conclusions: In future work, such forecasting models can be used to simulate different stages of recovery, dosages, and training schedules to optimize rehabilitation for each person. Trial registration This study contains a re-analysis of data from the DOSE clinical trial ID NCT01749358 and the EXCITE clinical trial ID NCT00057018.
    MeSH term(s) Humans ; Bayes Theorem ; Research Design ; Stroke ; Clinical Trials as Topic
    Language English
    Publishing date 2023-06-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2164377-5
    ISSN 1743-0003 ; 1743-0003
    ISSN (online) 1743-0003
    ISSN 1743-0003
    DOI 10.1186/s12984-023-01202-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article: Editorial: Model-informed decision making in the preclinical stages of pharmaceutical research and development.

    Li, Rui / Craig, Morgan / D'Argenio, David Z / Betts, Alison / Mager, Donald E / Maurer, Tristan S

    Frontiers in pharmacology

    2023  Volume 14, Page(s) 1184914

    Language English
    Publishing date 2023-04-12
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1184914
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Predicting monoclonal antibody pharmacokinetics following subcutaneous administration via whole-body physiologically-based modeling.

    Hu, Shihao / D'Argenio, David Z

    Journal of pharmacokinetics and pharmacodynamics

    2020  Volume 47, Issue 5, Page(s) 385–409

    Abstract: Use of the subcutaneous (SC) route for administering monoclonal antibodies (mAbs) to treat chronic conditions has been hindered because of an incomplete understanding of fundamental mechanisms controlling mAb absorption from the SC site, and due to the ... ...

    Abstract Use of the subcutaneous (SC) route for administering monoclonal antibodies (mAbs) to treat chronic conditions has been hindered because of an incomplete understanding of fundamental mechanisms controlling mAb absorption from the SC site, and due to the limited translatability of preclinical studies. In this paper, we report on the development and evaluation of a whole-body physiologically-based model to predict mAb pharmacokinetics following SC administration. The circulatory model is based on the physiological processes governing mAb transport and includes two mAb-specific parameters representing differences in pinocytosis rate and the diffusive/convective transport rates among mAbs. At the SC administration site, two additional parameters are used to represent mAb differences in lymphatic capillary uptake and in pre-systemic clearance. Model development employed clinical intravenous (IV) plasma PK data from 20 mAbs and SC plasma PK data from 12 of these mAbs, as obtained from the literature. The resulting model reliably described both the IV and SC measured plasma concentration data. In addition, a metric based on the positive charge across the mAb's complementarity determining region vicinity was found to positively correlate with the model-based estimates of the mAb-specific parameter governing organ/tissue pinocytosis transport and with estimates of the mAb's SC lymphatic capillary clearance. These two relationships were incorporated into the model and accurately predicted the SC PK profiles of three out of four separate mAbs not included in model development. The whole-body physiologically-based model reported herein, provides a platform to characterize and predict the plasma disposition of monoclonal antibodies following SC administration in humans.
    MeSH term(s) Administration, Intravenous ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacokinetics ; Chronic Disease/drug therapy ; Humans ; Injections, Subcutaneous ; Models, Biological ; Tissue Distribution
    Chemical Substances Antibodies, Monoclonal
    Language English
    Publishing date 2020-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041601-5
    ISSN 1573-8744 ; 1567-567X
    ISSN (online) 1573-8744
    ISSN 1567-567X
    DOI 10.1007/s10928-020-09691-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article: An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes

    Hu, Shihao / Lu, Yuzhi / Tura, Andrea / Pacini, Giovanni / D'Argenio, David Z

    Frontiers in endocrinology

    2021  Volume 12, Page(s) 641713

    Abstract: Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness ...

    Abstract Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (
    MeSH term(s) Adult ; Algorithms ; Anthropometry ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Female ; Glucose/therapeutic use ; Glucose Intolerance ; Glucose Tolerance Test ; Homeostasis ; Humans ; Insulin/therapeutic use ; Insulin Resistance ; Male ; Middle Aged ; Models, Statistical ; Models, Theoretical ; Young Adult
    Chemical Substances Blood Glucose ; Insulin ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-03-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2021.641713
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Analytical solution of linear multi-compartment models with non-zero initial condition and its implementation with R.

    D'Argenio, David Z / Bae, Kyun-Seop

    Translational and clinical pharmacology

    2019  Volume 27, Issue 2, Page(s) 43–51

    Abstract: The analytical solution for multi-compartment models with a non-zero initial condition is complex because of the inter-compartmental transfer. An elegant solution and its implementation in the 'wnl' R package can be useful in solving examples of ... ...

    Abstract The analytical solution for multi-compartment models with a non-zero initial condition is complex because of the inter-compartmental transfer. An elegant solution and its implementation in the 'wnl' R package can be useful in solving examples of textbooks and developing software of therapeutic drug monitoring, pharmacokinetic simulation, and parameter estimation. This solution uses Laplace transformation, convolution, matrix inversion, and the fact that the general solution of an inhomogeneous ordinary differential equation is the sum of a homogenous and a particular solution, together.
    Language English
    Publishing date 2019-06-28
    Publishing country Korea (South)
    Document type Journal Article ; Review
    ZDB-ID 2861878-6
    ISSN 2383-5427 ; 2289-0882
    ISSN (online) 2383-5427
    ISSN 2289-0882
    DOI 10.12793/tcp.2019.27.2.43
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Book ; Conference proceedings: Proceedings of the 1993 Biomedical Simulations Research Workshop on Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis

    D'Argenio, David Z.

    held May 21 - 22, 1993, in Los Angeles, California

    (Advanced methods of pharmacokinetic and pharmacodynamic systems analysis ; 2)

    1995  

    Event/congress Biomedical Simulations Research Workshop on Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis (1993, LosAngelesCalif.)
    Author's details ed. by David Z. D'Argenio
    Series title Advanced methods of pharmacokinetic and pharmacodynamic systems analysis ; 2
    Collection
    Keywords Pharmacokinetics / congresses ; Pharmacology / congresses
    Language English
    Size X, 217 S. : graph. Darst.
    Publisher Plenum Press
    Publishing place New York u.a.
    Publishing country United States
    Document type Book ; Conference proceedings
    HBZ-ID HT007336238
    ISBN 0-306-45018-6 ; 978-0-306-45018-1
    Database Catalogue ZB MED Medicine, Health

    Kategorien

To top