Publications (2)4.95 Total impact
-
Article: Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis
[show abstract] [hide abstract]
ABSTRACT: 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.British Journal of Clinical Pharmacology 10/2008; 50(6):605 - 613. · 2.96 Impact Factor -
Article: Latitude gradient influences the age of onset in rheumatoid arthritis patients.
[show abstract] [hide abstract]
ABSTRACT: The mean age of rheumatoid arthritis (RA) onset is around 50 years as reported in several clinical trials involving Caucasian patients. However, clinical observations suggest that Mexican RA patients' disease is initiated at a younger age. The objective of the study was to assess whether the age of onset of RA is different in Mexican and in Canadian RA patients. Certified rheumatologists from Canada and Mexico directly interviewed consecutive RA patients attending their clinics regarding the date patients first noticed a swollen joint. None of the participant rheumatologists were aware of the primary aim of this exploratory study at the time of the interviews. Data was gathered from 161 Mexican (91% women) and 130 Canadian (77% women) RA patients collected by three rheumatologists in each country. Duration since disease onset was not different within countries (mean 95% confidence interval [CI] for differences -10 to 16 years, p = 0.12 for Canadians, and -6 to 10 years, p = 0.26, for Mexicans). However, there was a significant difference between the two countries. Mexicans patients on average developed RA almost 12 years younger than Canadians (95% CI for difference 9 to 15 years, p < 0.001). Frequency distribution showed that 35.5% of Canadians but only 4% of Mexicans had the onset of the disease after the age of 55 (all p < 0.001). It appears that RA begins at a much younger age in Mexican than Canadian patients. If this were confirmed after controlling for different confounders and biases, it would have important societal, economic, and therapeutic implications.Clinical Rheumatology 11/2007; 26(10):1725-8. · 2.00 Impact Factor
