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The Effect of Oral Letermovir Administration on the Pharmacokinetics of a Single Oral Dose of P-Glycoprotein Substrate Digoxin in Healthy Volunteers.
Scheuenpflug, Jürgen; Kropeit, Dirk; Erb-Zohar, Katharina; Theis, Jochen G W; Stobernack, Hans-Peter; McCormick, David; Zimmermann, Holger; Rübsamen-Schaeff, Helga.
Afiliação
  • Scheuenpflug J; AiCuris Anti-infective Cures AG, Wuppertal, Germany.
  • Kropeit D; Merck KGaA, Darmstadt, Germany.
  • Erb-Zohar K; AiCuris Anti-infective Cures AG, Wuppertal, Germany.
  • Theis JGW; clinphase®, Schotten, Germany.
  • Stobernack HP; InHeCon, Bergisch Gladbach, Germany.
  • McCormick D; AiCuris Anti-infective Cures AG, Wuppertal, Germany.
  • Zimmermann H; AiCuris Anti-infective Cures AG, Wuppertal, Germany.
  • Rübsamen-Schaeff H; DMPK Solutions Ltd, Nottinghamshire, UK.
Clin Pharmacol Drug Dev ; 11(1): 6-15, 2022 01.
Article em En | MEDLINE | ID: mdl-34812580
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor approved in the United States, Canada, Japan, and the European Union for prophylaxis of CMV infection and disease in CMV-seropositive, allogeneic, hematopoietic stem-cell transplant recipients. In vitro, letermovir is a substrate and potential modulator of P-glycoprotein. The potential of letermovir to alter the pharmacokinetics of digoxin (a P-glycoprotein substrate) upon coadministration in healthy subjects was therefore investigated in a phase 1 trial (EudraCT: 2011-004516-39). Oral letermovir 240 mg was administered twice daily for 12 days with a single oral digoxin 0.5-mg dose on day 7; after a washout period, oral digoxin 0.5 mg was administered on day 35 (sequence 1). The period order was reversed after a 28-day washout for sequence 2. Pharmacokinetics and safety were evaluated. The presence of steady-state letermovir reduced digoxin area under the plasma concentration-time curve from administration until last quantifiable measurement by 12% and maximum plasma concentration by 22% compared with digoxin alone; digoxin half-life and elimination rate remained similar in both conditions. The between-subject variability of digoxin maximum plasma concentration was higher with letermovir than without (42% vs 31%) and similar for digoxin area under the plasma concentration-time curve in both periods. No specific safety or tolerability concerns were identified. Overall, letermovir had no clinically relevant effect on concomitant administration with digoxin.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinazolinas / Digoxina / Acetatos Limite: Humans País como assunto: America do norte Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinazolinas / Digoxina / Acetatos Limite: Humans País como assunto: America do norte Idioma: En Ano de publicação: 2022 Tipo de documento: Article