PMID- 32991788 OWN - NLM STAT- MEDLINE DCOM- 20211216 LR - 20211216 IS - 1099-1077 (Electronic) IS - 0885-6222 (Linking) VI - 36 IP - 1 DP - 2021 Jan TI - Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial. PG - 1-12 LID - 10.1002/hup.2761 [doi] AB - OBJECTIVE: To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. METHODS: Twenty-four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12-lead electrocardiogram were measured in supine position. AEs were also recorded. RESULTS: ARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs. CONCLUSIONS: OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects. CI - (c) 2020 John Wiley & Sons Ltd. FAU - Koller, Dora AU - Koller D AUID- ORCID: 0000-0002-0415-0466 AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Almenara, Susana AU - Almenara S AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Mejia, Gina AU - Mejia G AUID- ORCID: 0000-0002-8689-7941 AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. AD - UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Saiz-Rodriguez, Miriam AU - Saiz-Rodriguez M AUID- ORCID: 0000-0002-1660-3135 AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. AD - Research Unit, Fundacion Burgos por la Investigacion de la Salud, Hospital Universitario de Burgos, Burgos, Spain. FAU - Zubiaur, Pablo AU - Zubiaur P AUID- ORCID: 0000-0002-6150-4320 AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Roman, Manuel AU - Roman M AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. AD - UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Ochoa, Dolores AU - Ochoa D AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. AD - UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Wojnicz, Aneta AU - Wojnicz A AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Martin, Samuel AU - Martin S AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. AD - UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Romero-Palacian, Daniel AU - Romero-Palacian D AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Navares-Gomez, Marcos AU - Navares-Gomez M AUID- ORCID: 0000-0003-2501-6845 AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. FAU - Abad-Santos, Francisco AU - Abad-Santos F AUID- ORCID: 0000-0002-6519-8885 AD - Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teofilo Hernando, School of Medicine, Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. AD - UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigacion Sanitaria La Princesa (IP), Madrid, Spain. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200929 PL - England TA - Hum Psychopharmacol JT - Human psychopharmacology JID - 8702539 RN - 0 (Antipsychotic Agents) RN - 82VFR53I78 (Aripiprazole) RN - N7U69T4SZR (Olanzapine) SB - IM MH - Adult MH - Antipsychotic Agents/administration & dosage/adverse effects MH - Aripiprazole/*administration & dosage/*adverse effects MH - Blood Pressure/*drug effects MH - Dizziness/chemically induced MH - Electrocardiography MH - Female MH - Headache/chemically induced MH - Heart Rate/*drug effects MH - Humans MH - Male MH - Nausea/chemically induced MH - Olanzapine/*administration & dosage/*adverse effects MH - Sleepiness/drug effects OTO - NOTNLM OT - aripiprazole OT - cardiovascular effects OT - olanzapine OT - pharmacogenetics OT - safety EDAT- 2020/09/30 06:00 MHDA- 2021/12/17 06:00 CRDT- 2020/09/29 17:16 PHST- 2020/04/21 00:00 [received] PHST- 2020/09/09 00:00 [revised] PHST- 2020/09/14 00:00 [accepted] PHST- 2020/09/30 06:00 [pubmed] PHST- 2021/12/17 06:00 [medline] PHST- 2020/09/29 17:16 [entrez] AID - 10.1002/hup.2761 [doi] PST - ppublish SO - Hum Psychopharmacol. 2021 Jan;36(1):1-12. doi: 10.1002/hup.2761. Epub 2020 Sep 29.