PMID- 36282772
OWN - NLM
STAT- MEDLINE
DCOM- 20221027
LR  - 20221222
IS  - 1557-8992 (Electronic)
IS  - 1044-5463 (Linking)
VI  - 32
IP  - 8
DP  - 2022 Oct
TI  - Pharmacokinetics, Safety, and Tolerability of Cariprazine in Pediatric Patients 
      with Bipolar I Disorder or Schizophrenia.
PG  - 434-443
LID - 10.1089/cap.2021.0139 [doi]
AB  - Objective: Cariprazine is a dopamine D(3)-preferring D(3)/D(2) and serotonin 
      5-HT(1A) receptor partial agonist approved to treat adults with schizophrenia and 
      manic/mixed or depressive episodes associated with bipolar I disorder. This 
      sequential-cohort, dose-escalation study was the first to evaluate the 
      pharmacokinetic, safety, and tolerability profile of cariprazine and its two 
      major active metabolites, desmethyl-cariprazine (DCAR) and 
      didesmethyl-cariprazine (DDCAR), in pediatric patients with schizophrenia or 
      bipolar I disorder. Methods: This phase I open-label study enrolled patients with 
      schizophrenia (13-17 years of age) or bipolar I disorder (10-17 years of age). 
      Patients met the Diagnostic and Statistical Manual of Mental Disorders, Fifth 
      Edition (DSM-5) criteria for schizophrenia or bipolar I disorder and had Positive 
      and Negative Syndrome Scale (PANSS) total scores >/=70 or Young Mania Rating Scale 
      (YMRS) total scores >/=20. Patients were assigned to one of four treatment groups 
      to receive 6 weeks of cariprazine treatment through slow titration to 1.5, 3, or 
      4.5 mg/d or fast titration to 4.5 mg/d. Pharmacokinetics, adverse events (AEs), 
      and various safety parameters were analyzed. Efficacy was evaluated as an 
      exploratory outcome. Results: A total of 50 participants were enrolled. Based on 
      mean trough levels, steady state appeared to be reached within 1-2 weeks for 
      cariprazine and DCAR and within 4-5 weeks for DDCAR. Systemic exposure of 
      cariprazine, DCAR, and DDCAR generally increased approximately in proportion to 
      the increases in dose from 1.5 to 4.5 mg/d. The most frequent treatment-related, 
      treatment-emergent AEs included sedation, parkinsonism, tremor, dystonia, and 
      blurred vision. Improvements from baseline on the PANSS and YMRS were observed 
      throughout treatment. Conclusion: In this first investigation of cariprazine in a 
      pediatric population with schizophrenia or bipolar disorder, pharmacokinetic 
      parameters were consistent with those observed in adults. Cariprazine appeared to 
      be safe and tolerable in children and adolescents.
FAU - Riccobene, Todd
AU  - Riccobene T
AUID- ORCID: 0000-0002-3702-1097
AD  - AbbVie, Madison, New Jersey, USA.
FAU - Riesenberg, Robert
AU  - Riesenberg R
AD  - Atlanta Center for Medical Research, Atlanta, Georgia, USA.
FAU - Yeung, Paul P
AU  - Yeung PP
AD  - AbbVie, Madison, New Jersey, USA.
FAU - Earley, Willie R
AU  - Earley WR
AD  - AbbVie, Madison, New Jersey, USA.
FAU - Hankinson, Arlene L
AU  - Hankinson AL
AD  - AbbVie, Madison, New Jersey, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Child Adolesc Psychopharmacol
JT  - Journal of child and adolescent psychopharmacology
JID - 9105358
RN  - F6RJL8B278 (cariprazine)
RN  - 0 (Antipsychotic Agents)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - VTD58H1Z2X (Dopamine)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Child
MH  - Adolescent
MH  - *Bipolar Disorder/drug therapy/chemically induced
MH  - *Schizophrenia/drug therapy
MH  - *Antipsychotic Agents/adverse effects
MH  - Receptor, Serotonin, 5-HT1A/therapeutic use
MH  - Dopamine/therapeutic use
MH  - Serotonin
MH  - Treatment Outcome
OTO - NOTNLM
OT  - atypical antipsychotic
OT  - bipolar I disorder
OT  - cariprazine
OT  - pediatric
OT  - pharmacokinetic
OT  - schizophrenia
EDAT- 2022/10/26 06:00
MHDA- 2022/10/28 06:00
CRDT- 2022/10/25 13:13
PHST- 2022/10/25 13:13 [entrez]
PHST- 2022/10/26 06:00 [pubmed]
PHST- 2022/10/28 06:00 [medline]
AID - 10.1089/cap.2021.0139 [doi]
PST - ppublish
SO  - J Child Adolesc Psychopharmacol. 2022 Oct;32(8):434-443. doi: 
      10.1089/cap.2021.0139.