Anna Nordmark

SDS Life Science (Sweden)

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Stefan Lundgren

University of California, Davis

Fredrik Granath

Karolinska Institutet

Anders Rane

Agios Pharmaceuticals (United States)

Susan Cole

Pfizer (United Kingdom)

Sven Cnattingius

Karolinska Institutet

Eva Gil Berglund

Certara (United States)

Isabelle Ragueneau‐Majlessi

Certara (United States)

Tasha K. Ritchie

University of Washington

Savannah J. McFeely

Simcyp (United Kingdom)

Jingjing Yu

Certara (United States)

Cooperative Institutions

University of Florida

165

Columbus Oncology and Hematology Associates

161

Reckitt Benckiser (United States)

United States Food and Drug Administration

Karolinska Institutet

Center for Drug Evaluation and Research

Karolinska University Hospital

National Institutes of Health Clinical Center

AstraZeneca (Sweden)

John Wiley & Sons (United States)

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Caffeine Metabolism and the Risk of Spontaneous Abortion of Normal Karyotype Fetuses

Obstetrics and Gynecology (2001)

Lisa B. Signorello Anna Nordmark Fredrik Granath William J. Blot Joseph K. McLaughlin

In Brief OBJECTIVE To investigate whether the rate of caffeine metabolism influences spontaneous abortion risk. METHODS We studied 101 women with normal karyotype spontaneous abortions and 953 pregnant women at 6–12 gestational weeks. Participants reported on caffeine intake and provided urine for phenotyping cytochrome P4501A2 (CYP1A2) activity and blood for genotyping N-acetylation (NAT2) status. We calculated odds ratios (OR) and 95% confidence intervals (CI) to evaluate the association between each of the two metabolic indices and spontaneous abortion risk and also the potential interaction between caffeine intake and metabolic activity on such risk. In calculating the associations between the metabolic indices and risk of spontaneous abortion, we had 80% power to detect an OR of 2.1, with a Type I error of 0.05. RESULTS Slow acetylators had a nonsignificantly increased risk for spontaneous abortion (OR 1.36, 95% CI 0.84, 2.21) and recurrent spontaneous abortion (OR 2.51, 95% CI 0.81, 7.76). In contrast, low CYP1A2 activity was associated with a significantly decreased risk for spontaneous abortion (OR 0.35, 95% CI 0.20, 0.63). Caffeine was a risk factor for spontaneous abortion among women with high, but not low, CYP1A2 activity (OR 2.42, 95% CI 1.01, 5.80 for 100–299 mg/day; OR 3.17, 95% CI 1.22, 8.22 for 300 mg/day or more, among women with high CYP1A2 activity). CONCLUSION The findings indicate that high CYP1A2 activity may increase the risk of spontaneous abortion, independently or by modifying the effect of caffeine. The results regarding NAT2 are less conclusive but suggest that slow acetylators may be at elevated risk of spontaneous abortion. A rapid rate of caffeine metabolism, as measured by cytochrome P4501A2 phenotype, is associated with an increased risk of first-trimester normal karyotype spontaneous abortion.

10.1097/00006250-200112000-00013

Cite

Citations (4)

CYP3A and MDR1 (P-glycoprotein) gene expression levels along the human gastrointestinal tract

Basic & Clinical Pharmacology & Toxicology (2005)

Roberto Canaparo Anna Nordmark Niklas Finnström Stefan Lundgren Janeric Seidegård

P-glycoprotein

CYP3A

Human gastrointestinal tract

Source

Cite

Citations (0)

Scaling Dose-Exposure-Response from Adults to Children

Springer eBooks (2016)

Ine Skottheim Rusten Anna Nordmark Susan Cole Joseph F. Standing Sofia Friberg Hietala

Pharmacodynamics

Drug Development

10.1007/978-3-319-43754-5_7

Cite

Citations (1)

Plasma Folate Levels and Risk of Spontaneous Abortion

JAMA (2002)

Lena George James L. Mills Anna L.V. Johansson Anna Nordmark Bodil Olander

Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies.To study the association between plasma folate levels and the risk of spontaneous abortion.Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks.Risk of spontaneous abortion vs maternal plasma folate level.Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33).Low plasma folate levels were associated with an increased risk of early spontaneous abortion.

10.1001/jama.288.15.1867

Cite

Citations (242)

In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context

Molecular Pharmaceutics (2017)

Hans Lennernäs Anders Lindahl A. Van Peer Céline Ollier Talia Flanagan

The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.

Biopharmaceutical

Biopharmaceutics

IVIVC

10.1021/acs.molpharmaceut.6b00824

Cite

Citations (51)

Characterization of testosterone metabolism and 7-hydroxycoumarin conjugation by rat and human liver slices after storage in liquid nitrogen for 1 h up to 6 months

Xenobiotica (2002)

Charlotte Granhall E. Floby Anna Nordmark Arkadiusz Orzechowski A. Thörne

1. Slices of human and rat liver were cryopreserved in 18% dimethyl sulphoxide (DMSO) and subsequently stored in liquid nitrogen for periods up to as long as 6 months. After thawing, the metabolism of testosterone to hydroxylated products and conjugation of 7-hydroxycoumarin were investigated. 2. Rat liver slices stored in liquid nitrogen for 6 months exhibited rates of formation of 7alpha-, 6beta- 16alpha- and 2alpha-hydroxytestosterone, and of androstenedione that did not differ significantly from those observed with fresh slices. 3. No formation of 2alpha-hydroxytestosterone was detected with slices of human liver. However, in contrast with the rat, human slices produced 2beta-hydroxytestosterone. The rates of formation of 7alpha-, 6beta-, 16alpha- and 2beta-hydroxytestosterone and of androstenedione by human liver slices after 6 months of storage in liquid nitrogen were 82, 71, 236, 66 and 92%, respectively, of the corresponding rates by fresh slices. 4. The rates of sulphation and glucuronidation of 7-hydroxycoumarin by slices from rat liver were 97 and 119%, respectively, of the corresponding fresh values after 6 months of storage in liquid nitrogen. 5. 7-Hydroxycoumarin glucuronidation by human liver slices was 53% of the corresponding fresh values after 6 months of storage. However, human slices showed little or no capacity to conjugate 7-hydroxycoumarin with sulphate. 6. It was demonstrated that slices of both human and rat liver can be cryopreserved and stored in liquid nitrogen for at least 6 months without major changes in their rates of metabolism of testosterone to its hydroxylated products and of 7-hydroxycoumarin conjugation. These findings further emphasize that cryopreservation of liver slices can be an effective tool in the use of biological material of limited availability.

Liquid nitrogen

10.1080/0049825021000012646

Cite

Citations (8)

Towards Quantitation of the Effects of Renal Impairment and Probenecid Inhibition on Kidney Uptake and Efflux Transporters, Using Physiologically Based Pharmacokinetic Modelling and Simulations

Clinical Pharmacokinetics (2013)

Vicky Hsu Manuela de Lima Toccafondo Vieira Ping Zhao Lei Zhang Jenny Zheng

The kidney is a major drug-eliminating organ. Renal impairment or concomitant use of transporter inhibitors may decrease active secretion and increase exposure to a drug that is a substrate of kidney secretory transporters. However, prediction of the effects of patient factors on kidney transporters remains challenging because of the multiplicity of transporters and the lack of understanding of their abundance and specificity. The objective of this study was to use physiologically based pharmacokinetic (PBPK) modelling to evaluate the effects of patient factors on kidney transporters. Models for three renally cleared drugs (oseltamivir carboxylate, cidofovir and cefuroxime) were developed using a general PBPK platform, with the contributions of net basolateral uptake transport (Tup,b) and apical efflux transport (Teff,a) being specifically defined. We demonstrated the practical use of PBPK models to: (1) define transporter-mediated renal secretion, using plasma and urine data; (2) inform a change in the system-dependent parameter (≥10-fold reduction in the functional 'proximal tubule cells per gram kidney') in severe renal impairment that is responsible for the decreased secretory transport activities of test drugs; (3) derive an in vivo, plasma unbound inhibition constant of Tup,b by probenecid (≤1 μM), based on observed drug interaction data; and (4) suggest a plausible mechanism of probenecid preferentially inhibiting Tup,b in order to alleviate cidofovir-induced nephrotoxicity.

Probenecid

Efflux

10.1007/s40262-013-0117-y

Cite

Citations (84)

Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report

The AAPS Journal (2018)

Sandra Suarez‐Sharp Michael J. Cohen Filippos Kesisoglou Andreas Abend Patrick Marroum

IVIVC

Drug Development

10.1208/s12248-018-0252-3

Cite