Fukumura, Kazuya Yamada, Tadaaki Yokota, Takaaki Kawasaki, Akira
Published in
Clinical pharmacology in drug development
Naldemedine is a peripherally acting μ-opioid-receptor antagonist for the treatment of opioid-induced constipation. Two phase 1 single-dose studies investigated the pharmacokinetics and safety of a 0.2-mg oral dose of naldemedine in subjects with renal impairment (mild, n = 9; moderate, n = 9; severe, n = 6; and end-stage renal disease, n = 8) or h...
Weersink, Rianne A Burger, David M Hayward, Kelly L Taxis, Katja Drenth, Joost P H Borgsteede, Sander D
Published in
Expert opinion on drug metabolism & toxicology
Introduction: The global burden of cirrhosis is rising, and clinicians increasingly face the challenge of safely prescribing medicines for complications of hepatic disease and comorbidities. Prescribing in patients with cirrhosis is complicated by alterations that can occur in the pharmacology of medicines.Areas covered: This paper provides an over...
Malý, Ondřej Zajak, Ján Hyšpler, Radomír Turek, Zdeněk Astapenko, David Jun, Daniel Váňová, Nela Kohout, Aleš Radochová, Věra Kotek, Jiří
...
Published in
Annals of Translational Medicine
Background Liver resection is a surgical procedure associated with a high risk of hepatic failure that can be fatal. One of the key mechanisms involves ischemia-reperfusion damage. Building on the well-known positive effects of hydrogen at mitigating this damage, the goal of this work was to demonstrate the antioxidant, anti-inflammatory, and anti-...
Ng, Juki Duan, W Rachel Marbury, Thomas Schmidt, Jeffrey M Klein, Cheri E
Published in
Clinical pharmacology in drug development
The aim of these studies was to assess the safety and pharmacokinetics of elagolix, an oral nonpeptide gonadotropin-releasing hormone antagonist following oral administration in women with renal or hepatic impairment. Two phase 1 studies were conducted in adult women with normal renal function versus renal impairment (reduced study), and normal hep...
Weersink, Rianne A. Timmermans, Lotte Monster-Simons, Margje H. Mol, Peter G. M. Metselaar, Herold J. Borgsteede, Sander D. Taxis, Katja
Published in
Frontiers in Pharmacology
Background: In 2005, the European Medicines Agency (EMA) released guidance on pharmacokinetic studies in patients with hepatic impairment. This guidance describes the design of these studies and what information should be presented in the Summary of Product Characteristics (SmPC). We aim to evaluate the availability and clinical applicability of in...
Trueman, Sheryl Mohamed, Mohamed-Eslam F Feng, Tian Lacerda, Ana Paula Marbury, Thomas Othman, Ahmed A
Published in
Journal of clinical pharmacology
Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the treatment of several inflammatory autoimmune diseases, including rheumatoid arthritis. Upadacitinib is a nonsensitive substrate for metabolism by cytochrome P450 3A enzymes. This open-label, single-dose, multicenter study assessed the pharmacokinetics of upadacitinib follo...
Zhou, Xiaofei Lockhart, A Craig Fu, Siqing Nemunaitis, John Sarantopoulos, John Muehler, Andreas Rangachari, Lakshmi Bargfrede, Michael Venkatakrishnan, Karthik
Published in
Journal of clinical pharmacology
This clinical trial was designed to evaluate the effect of moderate or severe hepatic impairment on the single-dose pharmacokinetics (PK) of the investigational anticancer agent, alisertib, in adult patients with advanced solid tumors or lymphoma. Patients with normal hepatic function (total bilirubin and alanine transaminase [ALT] ≤ upper limit of...
Sun, Lei Yagoda, Sergey Du, Yangchun von Moltke, Lisa
Published in
Drug Design, Development and Therapy
Background A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain. Methods Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7–9 [c...
McNamara, Patrick J Meiman, Darius
Published in
Journal of pharmaceutical sciences
Plasma protein binding, namely the fraction unbound (fu), can be an important determinant of the disposition and response of drugs. The primary objective of this study was to predict fu values of 183 drugs utilizing either a single binding protein model, where the predominant binding protein had been established, or a multiple binding protein model...
Taylor, Lesley Crockett, Julie Tayo, Bola Morrison, Gilmour
Published in
Journal of clinical pharmacology
The pharmacokinetics and safety of a single oral dose of 200-mg plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD) in oral solution (Epidiolex in the United States; 100 mg/mL) were assessed in subjects with mild to severe hepatic impairment (n = 8 each for mild and moderate, n = 6 for severe) relative to matched subjects ...
