Author: Pieter Van Brantegem

A model-based evaluation of the effect of bosentan on bile salt disposition in sandwich-cultured human hepatocytes

Pieter Van Brantegem (1), Neel Deferm (1), Marlies Oorts (1), Axelle Cooreman (2), Mathieu Vinken (2), Erwin Dreesen (3, 4), Pieter Annaert (1)
(1) Drug Delivery and Disposition, KU Leuven, Belgium, (2) In Vitro Toxicology and Dermato-Cosmetology, VUB, Belgium, (3) Clinical Pharmacology and Pharmacotherapy, KU Leuven, Belgium, (4) Uppsala Pharmacometrics Research Group, Uppsala University, Sweden

Introduction Bosentan is an endothelin receptor antagonist used to treat patients with pulmonary arterial hypertension and is known to cause cholestatic liver toxicity. Bosentan is an inhibitor of the bile salt export pump (BSEP), the major efflux transporter for bile salts, but other mechanisms may also be involved. However, often high bosentan concentrations are used […]

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A population pharmacokinetic model of sildenafil in an extra-uterine system for premature lambs

Pieter Van Brantegem (1), Felix De Bie (2, 3), Francesca M. Russo (2), Erwin Dreesen (4, 5), Marcus G. Davey (3), Jan Deprest (2), Alan W. Flake (3), Pieter Annaert (1)
(1) Drug Delivery and Disposition, KU Leuven, Belgium, (2) Department of Development and Regeneration, KU Leuven, Belgium, (3) Center for Fetal Research, Children's Hospital of Philadelphia, USA, (4) Clinical Pharmacology and Pharmacotherapy, KU Leuven, Belgium, (5) Uppsala Pharmacometrics Research Group, Uppsala University, Sweden

Introduction Sildenafil is a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect on vascular smooth muscle cells [1]. Prenatal therapy with sildenafil has been studied for multiple indications in different animal models [2–4]. In pregnant sheep however, transplacental transfer of sildenafil is extremely low, which complicates the study of its effect on the fetus. […]

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