RT info:eu-repo/semantics/article
T1 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.
A1 Cuevas Castresana, Carlos de las
A1 Ruan, Can-Jun
A1 Ricciardi, Carina
A1 Schoretsanitis, Georgios
A1 Vincent, Philippe D.
A1 Anıl Yağcıoğlu, A. Elif
A1 Eap, Chin B.
A1 Baptista, Trino
A1 Clark, Scott R.
A1 Fernandez Egea, Emilio
A1 Kim, Se Hyun
A1 Lane, Hsien-Yuan
A1 Leung, Jonathan
A1 Maroñas Amigo, Olalla
A1 Motuca, Mariano
A1 Every-Palmer, Susanna
A1 Procyshyn, Ric M.
A1 Rohde, Christopher G.
A1 Suhas, Satish
A1 Schulte, Peter F. J.
A1 Schulte, Peter F. J.
A1 Spina, Edoardo
A1 Takeuchi, Hiroyoshi
A1 Verdoux, Hélène
A1 Correll, Christoph U.
A1 Molden, Espen
A1 De Leon, José
A2 Medicina InternaDermatología y Psiquiatría
A2 Adherencia Terapéutica
K1 clozapine/blood
K1 clozapine/metabolism
K1 clozapine/therapeutic use
K1 drug interaction
K1 medication adherence
K1 schizophrenia
AB Background: Up to 1/3 to 1/2 of outpatients prescribed clozapine may be partially or fully non-adherent, based on therapeutic drug monitoring (TDM). Three indices for measuring partial or full non-adherence are proposed: 1) a clozapine concentration/dose (C/D) ratio which drops to half or more of what is expected in the patient; 2) a clozapine/norclozapine ratio that becomes inverted; and 3) a clozapine concentration that becomes non-detectable. Methods: These 3 proposed indices are based on reviews of the literature and 3 samples which provided 15 cases of possible non-adherence. The three samples include: 1) an inpatient study in a Chinese hospital, 2) an inpatient randomized clinical trial in a United States hospital, and 3) and anoutpatient study in Uruguay. Results: Partial non-adherence in average patients can be suspected when the clozapine C/D ratio 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. Inverted clozapine/norclozapine ratios in the absence of alternative explanations may be a sign of non-adherence. 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 half or more of what is expected from the patient (around day 2); 2) the clozapine/norclozapine ratio becomes inverted (around day 3); and 3) the clozapine concentration became undetectable by the laboratory (around days 9-11). Conclusion: Future prospective studies should explore these proposed indices. Keywords: clozapine/blood; clozapine/metabolism; clozapine/therapeutic use; drug interaction; medication adherence; schizophrenia
SN 1573-2509
YR 2023
FD 2023
LK http://riull.ull.es/xmlui/handle/915/39601
UL http://riull.ull.es/xmlui/handle/915/39601
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 14-ene-2025