Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Hea
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ORIGINAL RESEARCH
Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics Dora Koller
. Susana Almenara . Gina Mejı´a . Miriam Saiz-Rodrı´guez .
Pablo Zubiaur . Manuel Roma´n . Dolores Ochoa . Marcos Navares-Go´mez . Elena Santos-Molina . Elena Pintos-Sa´nchez . Francisco Abad-Santos Received: October 21, 2020 / Accepted: November 7, 2020 Ó The Author(s) 2020
ABSTRACT Introduction: Aripiprazole and olanzapine are atypical antipsychotics. Both drugs can induce metabolic changes; however, the metabolic side effects produced by aripiprazole are more benign. The aim of the study was to evaluate if aripiprazole and olanzapine alter prolactin levels, lipid and glucose metabolism and Electronic Supplementary Material The online version of this article (https://doi.org/10.1007/s12325020-01566-w) contains supplementary material, which is available to authorized users. D. Koller S. Almenara G. Mejı´a M. SaizRodrı´guez P. Zubiaur M. Roma´n D. Ochoa M. Navares-Go´mez E. Santos-Molina E. Pintos-Sa´nchez F. Abad-Santos (&) Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teo´filo Hernando, School of Medicine, Universidad Auto´noma de Madrid, Instituto de Investigacio´n Sanitaria La Princesa (IP), Madrid, Spain e-mail: [email protected] G. Mejı´a M. Roma´n D. Ochoa E. Santos-Molina E. Pintos-Sa´nchez F. Abad-Santos UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigacio´n Sanitaria La Princesa (IP), Madrid, Spain M. Saiz-Rodrı´guez Research Unit, Fundacio´n Burgos Por La Investigacio´n de La Salud, Hospital Universitario de Burgos, Burgos, Spain
hepatic, haematological, thyroid and renal function. Methods: Twenty-four healthy volunteers received a daily oral dose of 10 mg aripiprazole and 5 mg olanzapine tablets for 5 days in a crossover randomised clinical trial and were genotyped for 51 polymorphisms in 18 genes by qPCR. Drug plasma concentrations were measured by LC–MS. The biochemical and haematological analyses were performed by enzymatic methods. Results: Olanzapine induced hyperprolactinaemia but aripiprazole did not. Dopamine D3 receptor (DRD3) Ser/Gly and ATP binding cassette subfamily B member 1 (ABCB1) rs10280101, rs12720067 and rs11983225 polymorphisms and cytochrome P450 3A (CYP3A) phenotype had an impact on plasma prolactin levels. C-peptide concentrations were higher after aripiprazole administration and were influenced by catechol-O-methyltransferase (COMT) rs4680 and rs13306278 polymorphisms. Olanzapine and the UDP glucuronosyltransferase family 1 member A1 (UGT1A1) rs887829 polymorphism were associated with elevated glucose levels. CYP3A poor metabolizers had increased insulin levels. Volunteers’ weight decreased significantly during aripiprazole treatment and a tendency for weight gain was observed during olanzapine treatment. Triglyceride concentrati
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