PMID- 32341640
OWN - NLM
STAT- MEDLINE
DCOM- 20210118
LR  - 20220414
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - The Effect of Liver and Kidney Disease on the Pharmacokinetics of Clozapine and 
      Sildenafil: A Physiologically Based Pharmacokinetic Modeling.
PG  - 1469-1479
LID - 10.2147/DDDT.S246229 [doi]
AB  - BACKGROUND AND OBJECTIVES: Physiologically based pharmacokinetic (PBPK) modeling 
      permits clinical scientists to reduce practical constraints for clinical trials 
      on patients with special diseases. In this study, simulations were carried out to 
      validate the pharmacokinetic parameters of clozapine and sildenafil using 
      Simcyp((R)) simulator in young male adults and compare the effect of renal or 
      hepatic impairment on the pharmacokinetic parameters of clozapine and sildenafil. 
      Also, the effect of age on pharmacokinetic parameters of both drugs was 
      investigated in healthy population and in patients with renal and hepatic 
      impairment. METHODS: A full PBPK model was built in the simulator for clozapine 
      and sildenafil based on physicochemical properties and observed clinical results. 
      The model used was Advanced, Dissolution, Absorption and Metabolism (ADAM) for 
      both drugs. RESULTS: The PBPK model adequately predicted the pharmacokinetic 
      parameters of clozapine and sildenafil for the healthy adult population. In the 
      simulation results, the bioavailability of both drugs was remarkably raised in 
      both renal and hepatic impairment in young and elderly populations. CONCLUSION: 
      PBPK modeling could be helpful in the investigation and comparison of the 
      pharmacokinetics in populations with specific disease conditions.
CI  - (c) 2020 Ghoneim and Mansour.
FAU - Ghoneim, Amira M
AU  - Ghoneim AM
AUID- ORCID: 0000-0003-2963-2135
AD  - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of 
      Pharmaceutical Sciences and Pharmaceutical Industries, Future University in 
      Egypt, Cairo, Egypt.
FAU - Mansour, Suzan M
AU  - Mansour SM
AUID- ORCID: 0000-0002-9235-7351
AD  - Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, 
      Cairo, Egypt.
AD  - Department of Pharmacology, Toxicology & Biochemistry, Faculty of Pharmaceutical 
      Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20200414
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Adult
MH  - Clozapine/*pharmacokinetics
MH  - Humans
MH  - Kidney Diseases/*metabolism
MH  - Liver Diseases/*metabolism
MH  - Male
MH  - Middle Aged
MH  - *Models, Biological
MH  - Sildenafil Citrate/*pharmacokinetics
MH  - Young Adult
PMC - PMC7166056
OTO - NOTNLM
OT  - clozapine
OT  - impairment
OT  - kidney
OT  - liver
OT  - physiologically based pharmacokinetic
OT  - sildenafil
COIS- The authors indicate that they have no conflicts of interest pertaining to the 
      content of this manuscript.
EDAT- 2020/04/29 06:00
MHDA- 2021/01/20 06:00
PMCR- 2020/04/14
CRDT- 2020/04/29 06:00
PHST- 2020/01/16 00:00 [received]
PHST- 2020/03/24 00:00 [accepted]
PHST- 2020/04/29 06:00 [entrez]
PHST- 2020/04/29 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/04/14 00:00 [pmc-release]
AID - 246229 [pii]
AID - 10.2147/DDDT.S246229 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Apr 14;14:1469-1479. doi: 10.2147/DDDT.S246229. 
      eCollection 2020.