Exploring low clozapine C/D ratios, inverted clozapine-norclozapine ratios and undetectable concentrations as measures of non-adherence in clozapine patients: A literature review and a case series of 17 patients from 3 studies - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Schizophrenia Research Année : 2023

Exploring low clozapine C/D ratios, inverted clozapine-norclozapine ratios and undetectable concentrations as measures of non-adherence in clozapine patients: A literature review and a case series of 17 patients from 3 studies

Can-Jun Ruan
  • Fonction : Auteur
Ismael Olmos
  • Fonction : Auteur
Carina Ricciardi
  • Fonction : Auteur
Georgios Schoretsanitis
  • Fonction : Auteur
Philippe D Vincent
  • Fonction : Auteur
a Elif Anil Yağcioğlu
  • Fonction : Auteur
Chin B Eap
  • Fonction : Auteur
Trino Baptista
  • Fonction : Auteur
Scott R Clark
  • Fonction : Auteur
Emilio Fernandez-Egea
  • Fonction : Auteur
Se Hyun Kim
  • Fonction : Auteur
Hsien-Yuan Lane
  • Fonction : Auteur
Jonathan Leung
  • Fonction : Auteur
Olalla Maroñas Amigo
  • Fonction : Auteur
Mariano Motuca
  • Fonction : Auteur
Susanna Every-Palmer
  • Fonction : Auteur
Ric M Procyshyn
  • Fonction : Auteur
Christopher Rohde
  • Fonction : Auteur
Satish Suhas
  • Fonction : Auteur
Peter F J Schulte
  • Fonction : Auteur
Edoardo Spina
  • Fonction : Auteur
Hiroyoshi Takeuchi
  • Fonction : Auteur
Christoph U Correll
  • Fonction : Auteur
Espen Molden
  • Fonction : Auteur
Carlos de las Cuevas
  • Fonction : Auteur
Jose de Leon
  • Fonction : Auteur

Résumé

Up to 1/2 of outpatients prescribed clozapine may be partially/fully non-adherent, based on therapeutic drug monitoring (TDM). Three indices for measuring partial/full non-adherence are proposed a: 1) clozapine concentration/dose (C/D) ratio which drops to half or more of what is expected in the patient; 2) clozapine/norclozapine ratio that becomes inverted; and 3) clozapine concentration that becomes non-detectable. These 3 proposed indices are based on a literature review and 17 cases of possible non-adherence from 3 samples: 1) an inpatient study in a Chinese hospital, 2) an inpatient randomized clinical trial in a United States hospital, and 3) and a Uruguayan outpatient study. The first index of non-adherence is a clozapine C/D ratio which is less than half the ratio corresponding to the patient's specific ancestry group and sex-smoking subgroup. Knowing the minimum therapeutic dose of the patient based on repeated TDM makes it much easier to establish non-adherence. The second index is inverted clozapine/norclozapine ratios in the absence of alternative explanations. The third index is undetectable concentrations. By using half-lives, the chronology of the 3 indices of non-adherence was modeled in two patients: 1) the clozapine C/D ratio dropped to ≥1/2 of what is expected from the patient (around day 2); 2) the clozapine/norclozapine ratio became inverted (around day 3); and 3) the clozapine concentration became undetectable by the laboratory (around days 9-11). Prospective studies should further explore these proposed clozapine indices in average patients, poor metabolizers (3 presented) and ultrarapid metabolizers (2 presented).
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Dates et versions

hal-04245813 , version 1 (17-10-2023)

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Can-Jun Ruan, Ismael Olmos, Carina Ricciardi, Georgios Schoretsanitis, Philippe D Vincent, et al.. Exploring low clozapine C/D ratios, inverted clozapine-norclozapine ratios and undetectable concentrations as measures of non-adherence in clozapine patients: A literature review and a case series of 17 patients from 3 studies. Schizophrenia Research, 2023, ⟨10.1016/j.schres.2023.07.002⟩. ⟨hal-04245813⟩

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