Jatinder Kaur Mukker

Ono Pharmaceutical (United States)

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Ioannis Gounaris

Merck (Germany)

Timothy A. Yap

The University of Texas MD Anderson Cancer Center

Anthony W. Tolcher

Texas Oncology

Johann S. de Bono

Institute of Cancer Research

Ruth Plummer

Newcastle University

Christine Hicking

Merck (Germany)

Giuseppe Locatelli

Merck (Germany)

Marta Enderlin

Merck (Germany)

Thomas Grombacher

Merck (Germany)

Zoltán Szűcs

Merck (United Kingdom)

Cooperative Institutions

Merck (Germany)

National Institute of Pharmaceutical Education and Research

Central Drug Research Institute

Academy of Scientific and Innovative Research

University of Florida

Takeda (United States)

Babasaheb Bhimrao Ambedkar University

Chandigarh University

National Institute of Pharmaceutical Education and Research

Jamia Hamdard

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Supplementary Methods S1 from First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors

Timothy A. Yap Anthony W. Tolcher Ruth Plummer Jatinder Kaur Mukker Marta Enderlin

Supplementary Methods

Solid tumor

10.1158/1078-0432.25826648.v1

Cite

Citations (0)

Supplementary Figure S4 from First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors

Timothy A. Yap Anthony W. Tolcher Ruth Plummer Jatinder Kaur Mukker Marta Enderlin

Figure S4. Tuvusertib PK/PD relationship.

Solid tumor

10.1158/1078-0432.25826651

Cite

Citations (0)

Ciclesonide: A Pro-Soft Drug Approach for Mitigation of Side Effects of Inhaled Corticosteroids

Journal of Pharmaceutical Sciences (2016)

Jatinder Kaur Mukker Ravi Shankar Prasad Singh Hartmut Derendorf

Ciclesonide

Active metabolite

Pharmacodynamics

10.1016/j.xphs.2016.05.004

Cite

Citations (18)

Determination of Atypical Nonlinear Plasma–Protein-Binding Behavior of Tigecycline Using an In Vitro Microdialysis Technique

Journal of Pharmaceutical Sciences (2014)

Jatinder Kaur Mukker Ravi Shankar Prasad Singh Hartmut Derendorf

Tigecycline

Ultrafiltration (renal)

Microdialysis

Bioanalysis

Analytical Ultracentrifugation

10.1002/jps.23872

Cite

Citations (28)

Data from First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors

Timothy A. Yap Anthony W. Tolcher Ruth Plummer Jatinder Kaur Mukker Marta Enderlin

<div>AbstractPurpose:Tuvusertib (M1774) is a potent, selective, orally administered ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. This first-in-human study (NCT04170153) evaluated safety, tolerability, maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of tuvusertib monotherapy.Patients and Methods:Ascending tuvusertib doses were evaluated in 55 patients with metastatic or locally advanced unresectable solid tumors. A safety monitoring committee determined dose escalation based on PK, PD, and safety data guided by a Bayesian 2-parameter logistic regression model. Molecular responses (MR) were assessed in circulating tumor DNA samples.Results:Most common grade ≥3 treatment-emergent adverse events were anemia (36%), neutropenia, and lymphopenia (both 7%). Eleven patients experienced dose-limiting toxicities, most commonly grade 2 (n = 2) or 3 (n = 8) anemia. No persistent effects on blood immune cell populations were observed. The RDE was 180 mg tuvusertib QD (once daily), 2 weeks on/1 week off treatment, which was better tolerated than the MTD (180 mg QD continuously). Tuvusertib median time to peak plasma concentration ranged from 0.5 to 3.5 hours and mean elimination half-life from 1.2 to 5.6 hours. Exposure-related PD analysis suggested maximum target engagement at ≥130 mg tuvusertib QD. Tuvusertib induced frequent MRs in the predicted efficacious dose range; MRs were enriched in patients with radiological disease stabilization, and complete MRs were detected for mutations in ARID1A, ATRX, and DAXX. One patient with platinum- and PARP inhibitor–resistant BRCA wild-type ovarian cancer achieved an unconfirmed RECIST v1.1 partial response.Conclusions:Tuvusertib demonstrated manageable safety and exposure-related target engagement. Further clinical evaluation of tuvusertib is ongoing.</div>

Solid tumor

10.1158/1078-0432.c.7234934

Cite

Citations (0)

Permeability and Conjugative Metabolism of Flaxseed Lignans by Caco-2 Human Intestinal Cells

Journal of Natural Products (2014)

Jatinder Kaur Mukker Déborah Michel Alister D. Muir Ed S. Krol Jane Alcorn

Reports in the literature associate the dietary intake of flaxseed lignans with a number of health benefits. The major lignan found in flaxseed, secoisolariciresinol diglucoside (1), undergoes metabolism principally to secoisolariciresinol (2), enterodiol (3), and enterolactone (4) in the human gastrointestinal tract. Systemically, lignans are present largely as phase II enzyme conjugates. To improve understanding of the oral absorption characteristics, a systematic evaluation of the intestinal permeation was conducted and the conjugative metabolism potential of these lignans using the polarized Caco-2 cell system was analyzed. For permeation studies, lignans (100 μM) were added to acceptor or donor compartments and samples were taken at 2 h. For metabolism studies, lignans (100 μM) were incubated in Caco-2 for a maximum of 48 h. Cell lysates and media were treated with β-glucuronidase/sulfatase, and lignan concentrations were determined using HPLC. Apical-to-basal permeability coefficients for 2–4 were 8.0 ± 0.4, 7.7 ± 0.2, and 13.7 ± 0.2 (×10–6) cm/s, respectively, whereas efflux ratios were 0.8–1.2, consistent with passive diffusion. The permeation of compound 1 was not detected. The extent of conjugation after 48 h was <3%, ∼95%, ∼90%, and >99% for 1–4, respectively. These data suggest 2–4, but not 1 undergo passive permeation and conjugative metabolism by Caco-2 cells.

Enterolactone

Caco-2

Intestinal Permeability

10.1021/np4004905

Cite

Citations (28)

Role of Divalent Metal Ions in Atypical Nonlinear Plasma Protein Binding Behavior of Tigecycline

Journal of Pharmaceutical Sciences (2016)

Ravi Shankar Prasad Singh Jatinder Kaur Mukker Amelia N. Deitchman Stephanie K. Drescher Hartmut Derendorf

Ethylenediaminetetraacetic acid

Tigecycline

Divalent

Free fraction

10.1016/j.xphs.2016.07.013

Cite

Citations (13)

A need to revisit clinical breakpoints of tigecycline: effect of atypical non-linear plasma protein binding

International Journal of Antimicrobial Agents (2017)

Ravi Shankar Prasad Singh Jatinder Kaur Mukker Stefanie K. Drescher Amelia N. Deitchman Hartmut Derendorf

Tigecycline

10.1016/j.ijantimicag.2016.12.008

Cite

Citations (18)

The pharmacokinetics of oral trazpiroben (TAK‐906) after organic anion transporting polypeptide 1B1/1B3 inhibition: A phase I, randomized study

Clinical and Translational Science (2022)

Jatinder Kaur Mukker George E. Dukes Max Tolkoff Lisi Wang Cristina Almansa

Trazpiroben is a dopamine D2 /D3 receptor antagonist under development for the treatment of gastroparesis. This phase I, open-label, randomized, two-way crossover study (NCT04121078) evaluated the effect of single-dose intravenous rifampin, a potent inhibitor of the organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on the pharmacokinetics and safety of trazpiroben in healthy adults. The utility of coproporphyrin (CP) I and CPIII as biomarkers of OATP inhibition was also assessed. Overall, 12 participants were enrolled and randomized (1:1) into one of two treatment sequences (AB and BA). Participants received either a single oral dose of trazpiroben 25 mg (treatment A) or a single oral dose of trazpiroben 25 mg immediately after a single 30-min intravenous infusion of rifampin 600 mg (treatment B). After a washout period of at least 7 days, participants received the other treatment. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞ ) and maximum serum concentration (Cmax ) of plasma trazpiroben were higher in participants receiving treatment B than those receiving treatment A (AUC∞ , 168.5 vs. 32.68 ng*h/ml; Cmax , 89.62 vs. 14.37 ng/ml); corresponding geometric mean ratios (90% confidence interval) showed 5.16 (4.25-6.25) and 6.24 (4.62-8.42)-fold increases in these parameters, respectively. In this study, trazpiroben was confirmed as a substrate of OATP1B1/1B3, and therefore co-administration of trazpiroben with moderate to strong inhibitors of OATP1B1/1B3 is not recommended. This is also the first assessment of the utility of CPI and CPIII as endogenous biomarkers of OATP1B1/1B3 inhibition after a single intravenous dose of rifampin.

Crossover study

Organic anion-transporting polypeptide

10.1111/cts.13274

Cite

Citations (6)

Pharmacokinetic and Pharmacodynamic Considerations in Elderly Population

AAPS advances in the pharmaceutical sciences series (2016)

Jatinder Kaur Mukker Ravinderjit Singh Hartmut Derendorf

Pharmacodynamics

10.1007/978-3-319-43099-7_10

Cite

Citations (9)