Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Sep 2019
Review Comparative StudyA focus on riociguat in the treatment of pulmonary arterial hypertension.
Current treatment of pulmonary arterial hypertension (PAH) targets three signalling pathways: the nitric oxide (NO) pathway, the endothelin pathway and the prostacyclin pathway. Riociguat is a soluble guanylate cyclase stimulator, acting via the NO pathway in a new way: unlike other common drugs targeting this pathway (eg tadalafil and sildenafil), riociguat acts independently of endogenous NO. This MiniReview focuses on PAH treatment with riociguat and on its advantages and disadvantages compared with other drugs targeting the NO pathway. ⋯ Moreover, riociguat has shown promising anti-proliferative, anti-inflammatory and anti-fibrotic effects in animal models. Further investigations are needed to determine whether this applies also to human beings. Taken together, riociguat induces vasodilation of the pulmonary arteries and leads to an improvement in the ability to carry out physical activity.
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Basic Clin. Pharmacol. Toxicol. · Aug 2019
Comparative StudyDifferences in preventing new-onset cardiovascular events with statin therapy in seniors aged 75 years and over: A cohort study in the South Korean National Health Insurance Database.
The aim of this cohort study was to compare the effectiveness of statin regimens for primary prevention among seniors aged ≥ 75 years. Seniors aged 75-100 years for whom statin therapies for primary prevention were newly initiated between 1 January 2009 and 31 December 2011, and who continued the same statin regimen during the first year after the index date were identified using the claims data from the South Korean National Health Insurance Database. A propensity score matching and multivariable Cox proportional hazards model were developed to evaluate adjusted ischaemic cardiovascular-cerebrovascular event (CCE) risk and all-cause mortality risk for all patients, as well as for subgroups. ⋯ For the 4689 older patients who regularly received moderate-intensity statin therapy including 10 mg atorvastatin, 20 mg atorvastatin, 10 mg rosuvastatin or 20 mg simvastatin for primary prevention, multivariable regression adjusting for potential covariates revealed no significant difference in ischaemic CCEs or all-cause mortality between the moderate-intensity statin users and 10 mg atorvastatin users both before and after propensity scoring matching. No significant heterogeneity was detected in the patient subgroups. The results of this study based on real-world data can supply evidence-based reasons for choice of statin regimen for the primary prevention of CCEs in older people aged ≥ 75 years.
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Basic Clin. Pharmacol. Toxicol. · Jun 2019
Retraction Of PublicationThe effect of 7-hydroxycoumarin on dextran sulfate sodium-induced ulcerative colitis.
C Wang, J Liu, Y Zhou, G Feng The above article from Basic & Clinical Pharmacology & Toxicology, published online on 26 December 2017 in Wiley Online Library (wileyonlinelibrary.com) as Accepted Article (https://doi.org/10.1111/bcpt.12948), has been withdrawn by agreement between the journal Editor in Chief Kim Brøsen, and John Wiley and Sons Ltd. The retraction has been agreed because the authors are not responding to requests to finalize their article for publication in the journal as the Version of Record.
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Basic Clin. Pharmacol. Toxicol. · May 2019
ReviewPharmacogenomics research and clinical implementation in Brazil.
We searched PubMed entries and the Lattes database of Brazilian Pharmacogenetics Network investigators, for pharmacogenetic/genomic (PGx) studies in the Brazilian population, focusing on the drugs and genes included in the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Warfarin was the most extensively studied drug in a PGx context: a genomewide association study targeting warfarin stable dose identified significant signals in VKORC1 and CYP2C9, several PGx dosing algorithms were developed based on these and other genes, and the implications of population admixture on extrapolation of dosing recommendations in the CPIC guidelines were examined. A study in renal transplanted patients disclosed association of CYP3A5*6 and CYP3A5*7 with tacrolimus dosing, which led to addition of these variants to CYP3A5*3 in the CPIC tacrolimus guideline. ⋯ No prospective analyses of drug therapy outcomes or cost-effectiveness assessments of PGx-guided therapy were found. In conclusion, the limited adoption of PGx-informed drug prescription in Brazil reflects combination of recognized barriers to PGx implementation worldwide plus factors specific to the Brazilian population. The latter include rarity/absence of genetic variants on which international PGx guidelines are based (eg HLA-B*15.02 for phenytoin and carbamazepine) and the caveat of extrapolating to the admixed Brazilian population, guidelines based on categorical variables, such as continental ancestry (eg warfarin guidelines), "race" or ethnicity.
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Basic Clin. Pharmacol. Toxicol. · Mar 2019
Extracorporeal treatments in poisonings from four non-traditionally dialysed toxins (acetaminophen, digoxin, opioids and tricyclic antidepressants): A combined single-centre and national study.
The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. ⋯ In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.