PMID- 34619548
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 41
DP  - 2021 Dec
TI  - Reduced theophylline clearance due to hepatic congestion secondary to right heart 
      failure - A population pharmacokinetic study.
PG  - 100403
LID - S1347-4367(21)00024-0 [pii]
LID - 10.1016/j.dmpk.2021.100403 [doi]
AB  - Theophylline, a beneficial drug with bronchodilatory and anti-inflammatory 
      effects, is used for the treatment of respiratory diseases. Pulmonary (PC) and 
      hepatic congestion (HC) are secondary to the development of left- and right-sided 
      heart failure (HF), respectively. This study aimed to evaluate the effects of PC 
      and HC on theophylline clearance (CL) by population pharmacokinetic (PPK) 
      analysis with consideration of the severity of HF assessed by the New York Heart 
      Association (NYHA) functional classification. We obtained 710 minimum 
      steady-state concentrations from 201 Japanese bronchial asthma patients with and 
      without HF. PPK analysis was performed by NONMEM. In the analysis, the left 
      ventricular ejection fraction, smoking (SMK), clarithromycin (CAM), sex, and age 
      were also considered as covariates. The final model of apparent theophylline 
      clearance (CL/F) was as follows: CL/F 
      (L/hr/kg) = 0.0465 x 1.40(SMK) x 0.870(CAM) x 0.863(HC(+)NYHA 
      II) x 0.634(HC(+)NYHA III) x 0.586(HC(-)NYHA IV) x 0.467(HC(+)NYHA IV). SMK is a 
      well-known factor that markedly enhances theophylline clearance through the 
      induction of CYP1A enzymes, while CAM has been reported to inhibit CYP3A4. The 
      final model indicates that HF patients with HC show reduced clearance of 
      theophylline depending on the severity of HF. In this study, no effects of PC 
      were observed.
CI  - Copyright (c) 2021 The Japanese Society for the Study of Xenobiotics. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Kurata, Yasuo
AU  - Kurata Y
AD  - Department of Pharmacy, Fukuoka City Hospital, Fukuoka City Hospital 
      Organization, Local Incorporated Administrative Agency, Fukuoka, Japan. 
      Electronic address: kurata.y@fcho.jp.
FAU - Muraki, Shota
AU  - Muraki S
AD  - Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Hirota, Takeshi
AU  - Hirota T
AD  - Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, Fukuoka, Japan; Department of Pharmacy, Kyushu 
      University Hospital, Fukuoka, Japan.
FAU - Araki, Hiroshi
AU  - Araki H
AD  - Department of Pharmacy, Fukuoka City Hospital, Fukuoka City Hospital 
      Organization, Local Incorporated Administrative Agency, Fukuoka, Japan.
FAU - Ieiri, Ichiro
AU  - Ieiri I
AD  - Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical 
      Sciences, Kyushu University, Fukuoka, Japan; Department of Pharmacy, Kyushu 
      University Hospital, Fukuoka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20210503
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - C137DTR5RG (Theophylline)
SB  - IM
MH  - *Heart Failure/drug therapy
MH  - Humans
MH  - Kinetics
MH  - Stroke Volume
MH  - *Theophylline
MH  - Ventricular Function, Left
OTO - NOTNLM
OT  - Heart failure
OT  - Hepatic congestion
OT  - New York heart association functional classification
OT  - Population pharmacokinetics
OT  - Theophylline clearance
COIS- Declaration of competing interest The authors have no conflicts of interest 
      directly relevant to the content of this article.
EDAT- 2021/10/08 06:00
MHDA- 2022/01/14 06:00
CRDT- 2021/10/07 20:26
PHST- 2021/01/15 00:00 [received]
PHST- 2021/04/23 00:00 [revised]
PHST- 2021/04/26 00:00 [accepted]
PHST- 2021/10/08 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/10/07 20:26 [entrez]
AID - S1347-4367(21)00024-0 [pii]
AID - 10.1016/j.dmpk.2021.100403 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2021 Dec;41:100403. doi: 10.1016/j.dmpk.2021.100403. 
      Epub 2021 May 3.