Meet the Experts Transporter Conference Webinar - Vitamin Transport in Clinical Toxicities:  Folate and Neural Tube Birth Defects

Meet the Experts Transporter Webinar - Vitamin Transport in Clinical Toxicities:  Folate and Neural Tube Birth Defects


Welcome


Like much of the world, we are limiting our travel and putting face-to-face meetings on hold as a result of the COVID-19 pandemic. The pace of scientific progress continues however, and with it the need for discourse and debate. Since taking the difficult decision to postpone our Meet the Experts Transporter Conference at the start of the year, we have received a significant level of interest from our colleagues in the transporter field for an alternative venue in which to showcase the latest in transporter research. We are therefore delighted to announce the start of the SOLVO Biotechnology Meet the Experts Transporter Webinar Series!


Speakers


ZAMEK-GLISZCZYNSKI Maciej, PhD

ZAMEK-GLISZCZYNSKI Maciej, PhD

Senior Fellow and Director, DMPK, GlaxoSmithKline, Collegeville, PA, USA

Biography

Maciej Zamek-Gliszczynski has 15 years of industry (Eli Lilly and GSK) experience in leading DMPK and PK/PD/clinical pharmacology aspects of oncology, endocrine/metabolic, and infectious disease programs at all stages between discovery, clinical development, and post-marketing (6 clinical candidate selections & INDs, 2 NDAs).  He is an experienced global manager, having led the Quantitative Drug Disposition group responsible for understanding victim and perpetrator DDIs for the entire GSK portfolio.  Dr. Zamek-Gliszczynski’s research is focused on PK/PD and DDI implications of drug and metabolite transport.  He is the author of >100 manuscripts and presentations on this subject (>5,000 cites, -index = 35).  He serves on the editorial boards of Pharmaceutical Research and Drug Metabolism and Disposition.  Dr. Zamek-Gliszczynski is a member of the International Transport Consortium (ITC) steering committee, was past chair of AAPS PK/PD/Drug Metabolism (PPDM) section, and he served as GSK management representative on IQ Translational ADME Leadership Group (TALG).  He has been active in organizing DMPK/clinical pharmacology meetings with ITC, ASCPT and AAPS.  Dr. Zamek-Gliszczynski lectures in graduate-level PK/PD courses and serves as external committee advisor (including as adjunct prof at UNC).  He enjoys developing scientists and has an established mentorship record at the associate scientist, junior and peer Ph.D., as well as graduate student and post-doc levels.


Abstract


Vitamin Transport in Clinical Toxicities:  Folate and Neural Tube Birth Defects

Preliminary analysis of ongoing birth surveillance study identified evidence of potential increased risk for neural-tube defects (NTDs) in newborns associated with exposure to dolutegravir at time of conception (Zash et al. 2008).  Folate deficiency is a common cause of NTDs.  Folate’s hydrophilic nature results in negligible passive membrane permeability and transport-mediated disposition.  Dolutegravir and other HIV integrase inhibitor drugs were evaluated for inhibition of folate transport pathways: proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and folate receptor α (FRα)-mediated endocytosis (Zamek-Gliszczynski et al., 2019).  Inhibition of folate transport was extrapolated to clinic using established approaches for transporters in intestine, distribution tissues, basolateral and apical membranes of renal proximal tubules (2017 FDA Guidance).  The present studies showed that dolutegravir is not a clinical inhibitor of folate transport pathways, and it is not predicted to elicit clinical decreases in maternal and fetal folate levels.  Furthermore, clinically-relevant HIV integrase inhibitor drug class effect on folate transport pathways was not observed.  Consistent with these findings, upon more complete enrollment of the birth surveillance study, dolutegravir no longer exhibited increased risk for NTDs (Zash et al., 2020).


Timing


Date: 29 September, 2020

8:00 am (PDT)

11:00 am (EDT)

4:00 pm (GMT)

5:00 pm (CET)

6:00 pm (IST)

11:00 pm (Beijing)

12:00 am (Tokyo, Seoul)


Recording


You can download the presentation slides here!