PMID- 31664765
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20210614
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 13
IP  - 2
DP  - 2020 Mar
TI  - Relationship Between Plasma Concentrations and Clinical Effects of Cariprazine in 
      Patients With Schizophrenia or Bipolar Mania.
PG  - 362-371
LID - 10.1111/cts.12720 [doi]
AB  - Population pharmacokinetic/pharmacodynamic modeling (via NONMEM) was used to 
      describe longitudinal exposure-response relationships for total cariprazine (sum 
      of cariprazine and its major active metabolites) in 2,558 patients with 
      schizophrenia or bipolar mania. Drug exposure metrics were explored for potential 
      relationships with efficacy and safety end points. Total cariprazine exposures 
      were significantly related to reductions in Positive and Negative Syndrome Scale 
      (PANSS) or Young Mania Rating Scale (YMRS) total scores in schizophrenia or 
      bipolar mania, respectively, via a maximum effect (E(max) )-type relationship. 
      Typical steady-state plasma concentrations after 3 and 4.5 mg/day were associated 
      with 50% of maximum typical reductions in PANSS and YMRS total scores, 
      respectively. Time-weighted cariprazine exposures had significant relationships 
      with the probability of common adverse events (AEs). Dose increase was associated 
      with increased efficacy but was also associated with an increase in AEs. Results 
      of these pharmacokinetic/pharmacodynamic analyses support that the recommended 
      dose range (1.5-6 mg/day for schizophrenia and 3-6 mg/day for bipolar mania) 
      provides an appropriate benefit-risk balance between cariprazine efficacy and 
      safety.
CI  - (c) 2019 Allergan. Clinical and Translational Science published by Wiley 
      Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Periclou, Antonia
AU  - Periclou A
AD  - Allergan, Madison, New Jersey, USA.
FAU - Willavize, Susan
AU  - Willavize S
AD  - Cognigen Corporation, Buffalo, New York, USA.
FAU - Jaworowicz, David
AU  - Jaworowicz D
AD  - Cognigen Corporation, Buffalo, New York, USA.
FAU - Passarell, Julie
AU  - Passarell J
AD  - Cognigen Corporation, Buffalo, New York, USA.
FAU - Carrothers, Timothy
AU  - Carrothers T
AD  - Allergan, Madison, New Jersey, USA.
FAU - Ghahramani, Parviz
AU  - Ghahramani P
AD  - Forest Research Institute, Inc., an Allergan affiliate, Jersey City, New Jersey, 
      USA.
FAU - Durgam, Suresh
AU  - Durgam S
AD  - Allergan, Madison, New Jersey, USA.
FAU - Earley, Willie
AU  - Earley W
AD  - Allergan, Madison, New Jersey, USA.
FAU - Kapas, Margit
AU  - Kapas M
AD  - Gedeon Richter Plc, Budapest, Hungary.
FAU - Khariton, Tatiana
AU  - Khariton T
AD  - Forest Research Institute, Inc., an Allergan affiliate, Jersey City, New Jersey, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191227
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Piperazines)
RN  - F6RJL8B278 (cariprazine)
SB  - IM
MH  - Adult
MH  - Antipsychotic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Bipolar Disorder/blood/diagnosis/*drug therapy
MH  - Clinical Trials as Topic
MH  - Datasets as Topic
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Piperazines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Psychiatric Status Rating Scales/statistics & numerical data
MH  - Risk Assessment
MH  - Schizophrenia/blood/diagnosis/*drug therapy
MH  - Treatment Outcome
PMC - PMC7070889
COIS- T.C., A.P., P.G., S.D., W.E., and T.K. are or were employees of Forest Research 
      Institute, Inc., an Allergan affiliate, at the time of the study. M.K. is an 
      employee of Gedeon Richter Plc. S.W., D.J., and J.P. were or are employees of 
      Cognigen, which was contracted by Forest Research Institute to perform the 
      analysis herein.
EDAT- 2019/10/31 06:00
MHDA- 2021/06/16 06:00
PMCR- 2020/03/01
CRDT- 2019/10/31 06:00
PHST- 2019/06/27 00:00 [received]
PHST- 2019/10/03 00:00 [accepted]
PHST- 2019/10/31 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2019/10/31 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - CTS12720 [pii]
AID - 10.1111/cts.12720 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2020 Mar;13(2):362-371. doi: 10.1111/cts.12720. Epub 2019 Dec 
      27.