Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis.
Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis.
复制标题
尽管类风湿性关节炎的药物浓度明显增加，但维拉帕米的促动力反应降低。
DOI：
--
复制
发表时间：
2000
影响因子：
3.4
通讯作者：
F. Jamali
中科院分区：
文献类型：
--
作者：
P. Mayo;K. Skeith;A. Russell;F. Jamali
AIMS
Inflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil.
METHODS
Eight RA patients were age- and sex-matched with eight healthy volunteers. The disease severity was assessed, and ECG, blood pressure and verapamil enantiomers concentrations were measured for 12 h post 80 mg oral verapamil. Serum interleukin-6 (IL-6) and nitrite (NO2-) were measured in predose samples.
RESULTS
IL-6 and NO2- concentrations were significantly increased in parallel with disease severity. Oral clearance of both S- and R-verapamil was significantly decreased by RA. While the unbound fraction of S- and R-verapamil decreased by 5 and 7-fold, respectively, the unbound AUC remained unchanged for the more potent enantiomer, S-verapamil. AUC of norverapamil enantiomers was increased 2-3-fold. Despite elevated serum drug concentrations in RA, the potential to prolong the PR-interval was significantly reduced by one fold and the effect on the heart rate and blood pressure did not increase.
CONCLUSIONS
RA results in increased verapamil concentrations due likely to changes in protein binding, decreased clearance and/or altered hepatic blood flow. A significant decrease in dromotropic effect, despite increased serum drug concentrations, may be attributed to receptor down regulation caused by pro-inflammatory cytokines and/or NO.
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影响因子：
3.4
作者：
Tracy, TS;Korzekwa, KR;Wainer, IW
通讯作者：
Wainer, IW
炎症介质对急性期基因表达的调节。
DOI：
--
发表时间：
1987
期刊：
Molecular biology & medicine
影响因子：
--
作者：
Fey,GH;Fuller,GM
通讯作者：
Fuller,GM
外消旋维拉帕米给药期间的立体选择性维拉帕米处置和衰老动力学。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Abernethy,DR;Wainer,IW;Longstreth,JA;Andrawis,NS
通讯作者：
Andrawis,NS
影响因子：
56.9
作者：
FINKEL, MS;ODDIS, CV;SIMMONS, RL
通讯作者：
SIMMONS, RL
DOI：
10.1073/pnas.90.23.11147
发表时间：
1993-12-01
影响因子：
11.1
作者：
KHATSENKO, OG;GROSS, SS;VANE, JR
通讯作者：
VANE, JR