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1.
Expert Opin Drug Saf ; 19(1): 1-8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855607

RESUMO

Introduction: Hypoactive sexual desire disorder (HSDD) is the most prevalent sexual dysfunction in women, previously managed with off-label therapies. Indicated for premenopausal women, flibanserin is the first FDA-approved medication to treat HSDD.Areas covered: This review summarizes flibanserin's pharmacokinetics, proposed mechanism of action, and safety data in clinical trials with a focus on sedation- and hypotension-related adverse events, and drug interactions with alcohol and antidepressants. Sources included peer-reviewed publications and internal data from the manufacturer.Expert opinion: Flibanserin is a well-tolerated and effective treatment that decreases distress and restores sexual desire to a level that is normative for the individual patient with HSDD. Simplification of a risk mitigation program for flibanserin in the US is likely to increase the number of prescribing clinicians if accompanied with educational efforts to clarify flibanserin's risk-benefit profile. As flibanserin is dosed daily and may be used for a decade or more in the typical premenopausal patient, long-term pharmacovigilance data will be essential. Over time, HSDD will be treated by more nonspecialist health care professionals and flibanserin will likely become established as a significant treatment option along with other medications approved for this indication in the context of a holistic biopsychosocial treatment paradigm.


Assuntos
Benzimidazóis/administração & dosagem , Pré-Menopausa , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Benzimidazóis/efeitos adversos , Interações de Medicamentos , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia
3.
Expert Opin Drug Metab Toxicol ; 15(11): 927-935, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668105

RESUMO

Introduction: Ritonavir and cobicistat are pharmacoenhancers used to improve the disposition of other HIV antiretrovirals. These drugs are, however, characterized by important pharmacokinetic differences.Areas covered: Here, the authors firstly update the available information on the pharmacokinetics of ritonavir and cobicistat. Subsequently, the review focuses on the description of drug-drug interactions (DDIs) involving cobicistat and comedications that might beneficiate from a shift-back to ritonavir. A MEDLINE Pubmed search for articles published from January 1995 to April 2019 was completed matching the term ritonavir or cobicistat with pharmacokinetics, DDIs, and pharmacology. Moreover, additional studies were identified from the reference list of retrieved articles.Expert opinion: Despite more than 20 years after its introduction on the market, ritonavir still represents a valid option for the treatment of selected HIV-infected patients. The large-scale switch to cobicistat may result in some unexpected DDIs not previously reported for ritonavir. Besides the issue of DDIs, additional advantage of ritonavir over cobicistat is its use in pregnancy, and its availability as single component of pharmaceutical formulations allowing the fine-tuning of antiretroviral regimens in patients with heavy polypharmacy when other unboosted-based therapeutic options cannot be used.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Cobicistat/administração & dosagem , Ritonavir/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Cobicistat/farmacocinética , Interações de Medicamentos , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Ritonavir/farmacocinética
4.
Medicina (B Aires) ; 79 Suppl 3: 48-53, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31603844

RESUMO

Antiepileptic drugs are the first treatment option in patients with epilepsy. Drugs developed after 2000 are known as third generation antiepileptic drugs. These medications offer new mechanisms of action and favorable pharmacokinetics, decreasing the occurrence of side effects and drug-drug interactions. Broad spectrum antiepileptic drugs, such as brivaracetam and clobazam are good choices for generalized tonic colonic seizures and are well tolerated.New sodium channel blockers such as lacosamide and eslicarbazepine, have a more "benign" side effect profile than the first or second generation of sodium channel blockers. These new drugs are useful therapies in patients with epilepsy of difficult control. Cannabidiol and fenfluramine are useful in the treatment of Dravet or Lennox Gastaut syndrome. Allopregnenolona and ganaxolone showed good efficacy in status epilepticus and could play an important future role in this clinical scenario.


Assuntos
Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/classificação , Interações de Medicamentos , Humanos , Estado Epiléptico/tratamento farmacológico
6.
Expert Opin Drug Metab Toxicol ; 15(10): 803-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595800

RESUMO

Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. Areas covered: This review introduces phase II/III of clinical trials related with Tac's roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients. Expert opinion: A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/administração & dosagem , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacocinética , Interações de Medicamentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Farmacogenética , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética
7.
Nihon Yakurigaku Zasshi ; 154(4): 210-216, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597901

RESUMO

Drug transporters play important roles in determining drug pharmacokinetics. Organic anion transporting polypeptides 1B1/1B3 (OATP1B1/1B3) are transporters mediating hepatic uptake of various anionic drugs. OATP1B1/1B3 activities are changed by genetic mutation and drug-drug interaction (DDI) that could lead to severe adverse reactions. Methods to address the precise DDI risk assessment have been developed in addition to the translational assessment from the results of in vitro studies. Using endogenous substrates as probes is an emerging approach that allows clinical assessment of the DDI risk in the early phase of drug development. Then, the clinical data will be subjected to the pharmacokinetic analysis using physiologically-based pharmacokinetic models to perform the more realistic DDI risk assessment with OATP1B1/1B3 substrate drugs. When drug targets are located inside the hepatocytes, DDI impact on the intrahepatic concentration is critical for their pharmacological actions. Positron emission tomography (PET) allows researchers to determine tissue concentration time profiles of the PET probe upon the inhibition of OATP1B1/1B3, and to estimate the change in kinetic parameter for each intrinsic process of hepatic elimination of PET probe. Integration of the clinical data into the PBPK model realizes more precise prediction of DDI impact on the pharmacokinetics of drugs, and their therapeutic effects.


Assuntos
Interações de Medicamentos , Transportador 1 de Ânion Orgânico Específico do Fígado/fisiologia , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/fisiologia , Humanos , Farmacocinética , Tomografia por Emissão de Pósitrons
8.
Adv Exp Med Biol ; 1141: 341-360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571169

RESUMO

The kidney plays an important role in maintaining total body homeostasis and eliminating toxic xenobiotics and metabolites. Numerous drugs and their metabolites are ultimately eliminated in the urine. The reabsorption and secretion functions of the nephron are mediated by a variety of transporters located in the basolateral and luminal membranes of the tubular cells. In the past decade, many studies indicated that transporters play important roles in drug pharmacokinetics and demonstrated the impact of renal transporters on the disposition of drugs, drug-drug interactions, and nephrotoxicities. Here, we focus on several important renal transporters and their roles in drug elimination and disposition, drug-induced nephrotoxicities and potential clinical solutions.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Rim , Proteínas de Membrana Transportadoras , Preparações Farmacêuticas , Animais , Transporte Biológico , Interações de Medicamentos , Humanos , Inativação Metabólica , Rim/efeitos dos fármacos , Preparações Farmacêuticas/metabolismo
9.
Adv Exp Med Biol ; 1141: 361-405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571170

RESUMO

Oral drug administration is the most favorable route of drug administration in the clinic. Intestinal transporters have been shown to play a significant role in the rate and extent of drug absorption of some, but not all, drug molecules. Due to the heterogeneous expression of multiple transporters along the intestine, the preferential absorption sites for drugs may vary significantly. In this chapter, we aim to summarize the current research on the expression, localization, function, and regulation of human intestinal transporters implicated in altering the absorption of low to medium molecular weight drug molecules. The role played by bile acid transport proteins (e.g., ASBT and OST-α/ß) is included in the discussion. The synergistic action of intestinal drug metabolism and transport is also discussed. Despite the complicated regulatory factors, the biopharmaceutics drug disposition classification system (BDDCS) put forward by Wu and Benet may help us better predict the effect of transporters on drug absorption. The drug-induced toxicity in the intestine, which may result from drug-drug interaction, gut microbiota, and bile salt toxicity, is also discussed.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Absorção Intestinal , Intestinos , Proteínas de Membrana Transportadoras , Preparações Farmacêuticas , Interações de Medicamentos , Humanos , Intestinos/efeitos dos fármacos , Preparações Farmacêuticas/metabolismo
10.
Expert Opin Drug Metab Toxicol ; 15(10): 849-867, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31566028

RESUMO

Introduction: Piperine, the major bioactive component from black pepper, has gained increasing attention for its beneficial effects in the central nervous system (CNS). However, its related pharmacodynamics and brain pharmacokinetics, as well as its interaction with other CNS drugs are lacking, which may hinder its therapeutic and safe use. Areas covered: The current review provides an updated summary on CNS activities of piperine, including anti-epileptic, anti-depressive and neurodegeneration protection effect. The brain pharmacokinetic properties of piperine together with the approaches to enhance its aqueous solubility were summarized. Considering the wide use of black pepper and the well-reported alteration on CYP and transporters by piperine, interactions between piperine and CNS drugs are also illustrated for the first time. Expert opinion: Although the CNS beneficial effects of piperine have been extensively studied in preclinical models, clinical evidence on its CNS application is barely available, which may be attributed to its limited aqueous solubility, unclear pharmacokinetic properties in humans and potential toxicities during long-term use at higher doses. Although beneficial interactions between piperine and certain CNS drugs were often reported in preclinical studies, more mechanistic studies with clinically relevant doses should be conducted to provide guidance on their clinical combination use.


Assuntos
Alcaloides/farmacologia , Benzodioxóis/farmacologia , Doenças do Sistema Nervoso Central/tratamento farmacológico , Piper nigrum/química , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/farmacocinética , Animais , Benzodioxóis/isolamento & purificação , Benzodioxóis/farmacocinética , Fármacos do Sistema Nervoso Central/isolamento & purificação , Fármacos do Sistema Nervoso Central/farmacocinética , Fármacos do Sistema Nervoso Central/farmacologia , Doenças do Sistema Nervoso Central/fisiopatologia , Relação Dose-Resposta a Droga , Interações de Medicamentos , Humanos , Piperidinas/isolamento & purificação , Piperidinas/farmacocinética , Alcamidas Poli-Insaturadas/isolamento & purificação , Alcamidas Poli-Insaturadas/farmacocinética
11.
Pharm Res ; 36(12): 170, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654151

RESUMO

PURPOSE: Many bioactive molecules show a type of solution phase behavior, termed promiscuous aggregation, whereby at micromolar concentrations, colloidal drug-rich aggregates are formed in aqueous solution. These aggregates are known to be a major cause of false positives and false negatives in select enzymatic high-throughput screening assays. The goal of this study was to investigate the impact of drug-rich aggregates on in vitro drug screening metabolism assays. METHODS: Cilnidipine was selected as an aggregate former and its impact on drug metabolism was evaluated against rCYP2D6, rCYP1A2, rCYP2C9 and human liver microsomes. RESULTS: The cilnidipine aggregates were shown to non-specifically inhibit multiple cytochrome P450 enzymes with an IC50 comparable with the IC50 of potent model inhibitors. CONCLUSIONS: This newly demonstrated mode of "promiscuous inhibition" is of great importance as it can lead to false positives during drug metabolism evaluations and thus it needs to be considered in the future to better predict in vivo drug-drug interactions.


Assuntos
Sistema Enzimático do Citocromo P-450/química , Di-Hidropiridinas/química , Microssomos Hepáticos/metabolismo , Proteínas Recombinantes/química , Carvedilol/química , Carvedilol/metabolismo , Coloides/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Diclofenaco/química , Diclofenaco/metabolismo , Di-Hidropiridinas/metabolismo , Interações de Medicamentos , Ensaios de Triagem em Larga Escala/métodos , Humanos , Concentração Inibidora 50 , Cinética , Taxa de Depuração Metabólica/efeitos dos fármacos , Fenacetina/química , Fenacetina/metabolismo , Proteínas Recombinantes/metabolismo , Solventes/química , Tamoxifeno/química , Tamoxifeno/metabolismo
12.
Expert Opin Drug Metab Toxicol ; 15(10): 779-785, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593639

RESUMO

Introduction: Interferon (IFN) had both antiviral and immunomodulatory effects, and was one of the approved treatments for hepatitis B virus (HBV). Herein, we reviewed the pharmacokinetics and pharmacodynamics of pegylated IFN-α (PegIFN-α) for the treatment of HBV. Areas covered: The steady-state serum levels of PegIFN-α were reached within 5 to 8 weeks, and the week 48 mean trough concentrations were approximately 2-fold higher than week 1. There was also no difference of the pharmacokinetics in male or female, healthy volunteers or patients with hepatitis B or C infection. PegIFN-α did not affect the metabolism of the cytochrome P450 (CYP) isozymes, except inhibition of CYP1A2. There was also no pharmacokinetic interaction between PegIFN-α and HBV nucleot(s)ide analogues (NUCs). Forty-eight weeks of PegIFN-α achieved 32% of HBeAg seroconversion, 32-43% of HBV DNA suppression, 41-59% of ALT normalization, and 3% of HBsAg seroconversion rate with a post-treatment durable response up to 80% in the initial responders. Expert opinion: On-treatment HBsAg titer guided the treatment of HBV with PegIFN-α. The recommendation of PegIFN-α and NUC combination or switch remained controversial. New immunotherapeutic agents are now in development. Although, PegIFN-α should continue to play a role in the treatment of HBV.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/farmacologia , DNA Viral/efeitos dos fármacos , Interações de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Humanos , Interferon alfa-2/farmacocinética , Interferon alfa-2/farmacologia , Interferon-alfa/farmacocinética , Interferon-alfa/farmacologia , Masculino , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia
13.
Adv Exp Med Biol ; 1141: 203-240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571166

RESUMO

Transporters play an important role in the absorption, distribution, metabolism, and excretion (ADME) of drugs. In recent years, various in vitro, in situ/ex vivo, and in vivo methods have been established for studying transporter function and drug-transporter interaction. In this chapter, the major types of in vitro models for drug transport studies comprise membrane-based assays, cell-based assays (such as primary cell cultures, immortalized cell lines), and transporter-transfected cell lines with single transporters or multiple transporters. In situ/ex vivo models comprise isolated and perfused organs or tissues. In vivo models comprise transporter gene knockout models, natural mutant animal models, and humanized animal models. This chapter would be focused on the methods for the study of drug transporters in vitro, in situ/ex vivo, and in vivo. The applications, advantages, or limitations of each model and emerging technologies are also mentioned in this chapter.


Assuntos
Proteínas de Membrana Transportadoras , Projetos de Pesquisa , Animais , Transporte Biológico , Linhagem Celular , Interações de Medicamentos , Humanos , Técnicas In Vitro , Projetos de Pesquisa/tendências
14.
Adv Exp Med Biol ; 1141: 241-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571167

RESUMO

Drug transporters are considered to be determinants of drug disposition and effects/toxicities by affecting the absorption, distribution, and excretion of drugs. Drug transporters are generally divided into solute carrier (SLC) family and ATP binding cassette (ABC) family. Widely studied ABC family transporters include P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance proteins (MRPs). SLC family transporters related to drug transport mainly include organic anion-transporting polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), organic cation/carnitine transporters (OCTNs), peptide transporters (PEPTs), and multidrug/toxin extrusions (MATEs). These transporters are often expressed in tissues related to drug disposition, such as the small intestine, liver, and kidney, implicating intestinal absorption of drugs, uptake of drugs into hepatocytes, and renal/bile excretion of drugs. Most of therapeutic drugs are their substrates or inhibitors. When they are comedicated, serious drug-drug interactions (DDIs) may occur due to alterations in intestinal absorption, hepatic uptake, or renal/bile secretion of drugs, leading to enhancement of their activities or toxicities or therapeutic failure. This chapter will illustrate transporter-mediated DDIs (including food drug interaction) in human and their clinical significances.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Interações de Medicamentos , Preparações Farmacêuticas , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transporte Biológico , Interações Alimento-Droga , Humanos , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos , Preparações Farmacêuticas/metabolismo
15.
BMC Infect Dis ; 19(1): 834, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601174

RESUMO

BACKGROUND: Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function. METHODS: We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF. RESULTS: We included 5'012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2'796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07-1.50), age > 50 years (1.43, 1.23-1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77-2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09-0.13), those treated in non-tertiary care centers (0.56, 0.46-0.70), as well as those with CD4 cell counts below 500/µL (0.77, 0.66-0.90) and with chronic hepatitis C infection (0.66, 0.54-0.80) were most likely to stay on TDF. CONCLUSIONS: Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adenina/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Interações de Medicamentos , Feminino , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suíça , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
16.
Expert Opin Drug Metab Toxicol ; 15(11): 975-984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619082

RESUMO

Objectives: Riociguat is a soluble guanylate cyclase stimulator licensed for the treatment of pulmonary arterial hypertension (PAH), a potentially fatal complication of human immunodeficiency virus infection. This study investigated the inhibitory potency of selected antiretroviral regimens on the metabolic clearance of riociguat.Methods: The inhibitory potential of the components of six antiretroviral combinations (ATRIPLA® (efavirenz/emtricitabine/tenofovir disoproxil), COMPLERA® (rilpivirine/emtricitabine/tenofovir disoproxil), STRIBILD® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil), TRIUMEQ® (abacavir/dolutegravir/lamivudine), and two ritonavir-boosted regimens) on riociguat metabolism were evaluated in recombinant human CYP1A1 and CYP3A4 as well as in human hepatocytes exhibiting both CYP1A1 and CYP3A4 activity. In vitro-in vivo correlation was performed between calculated and observed increases in riociguat exposure in vivo.Results: Using both in vitro systems, the predicted increase in exposure of riociguat was highest with components of TRIUMEQ® followed by COMPLERA®, ATRIPLA®, STRIBILD®, and the ritonavir-boosted regimens. Further experiments in human hepatocytes confirmed CYP1A1 to be the predominant enzyme in the metabolic clearance of riociguat.Conclusion: Antiretroviral treatment containing the potent CYP1A1 inhibitor abacavir had the greatest impact on riociguat metabolic clearance. The impact of comedications containing only strong CYP3A4 inhibitors e.g. ritonavir was less pronounced, suggesting a benefit of riociguat over PAH-targeting medications with contraindications for use with strong CYP3A4 inhibitors.


Assuntos
Fármacos Anti-HIV/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Ativadores de Enzimas/metabolismo , Pirazóis/metabolismo , Pirimidinas/metabolismo , Fármacos Anti-HIV/administração & dosagem , Citocromo P-450 CYP1A1/antagonistas & inibidores , Citocromo P-450 CYP3A/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/farmacologia , Interações de Medicamentos , Ativadores de Enzimas/administração & dosagem , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Humanos , Técnicas In Vitro , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem
17.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 11(5): 1312-1318, out.-dez. 2019. ilus
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1022225

RESUMO

Objective: The study's purpose has been to relate the drug interactions of oral anticoagulants with other medications used by elderly people hospitalized in a cardiology hospital. Methods: It is a prospective exploratory study with 16 elderly people taking oral anticoagulant, who were hospitalized at a governmental cardiology institution in São Paulo State over the period from November to December 2017. Results: Among 73 medicines prescribed and analyzed in the Micromedex 2.0, 24 (33.3%) interacted with Warfarin, the only prescribed oral anticoagulant. There were found Omeprazole (70; 97.2%); Dipyrone (68; 94.4%); Simvastatin (43; 59.72%); Enoxaparin (42; 58.33%); Amiodarone (29; 40.27%); Sertraline (28; 38.88%); Spironolactone (21; 29.16%); and Atenolol (11; 15.27%), whose interactions could either potentialize or inhibit the anticoagulant action. Considering the interactions, 14 (58.33%) were of moderate severity, 10 (41.66%) of high severity and 14 (58.33%) of fast effect. Conclusion: Polypharmacy and the use of oral anticoagulants in elderly patients bearing heart diseases are common events. Moreover, a better understanding about drug interactions is also required, bearing in mind that they can either potentialize or decrease the anticoagulant effect, with high or moderate severity


Objetivo: Relacionar as interações medicamentosas dos anticoagulantes orais com os medicamentos utilizados por idosos internados em hospital cardiológico. Método: Estudo exploratório, prospectivo, com 16 idosos em uso de anticoagulantes orais, internados numa instituição cardiológica governamental de São Paulo entre novembro e dezembro de 2017. Resultados: Dentre 73 medicamentos prescritos e analisados no Micromedex 2.0, 24 (33,3%) interagiam com a Varfarina, único anticoagulante oral prescrito. Encontrou-se Omeprazol (70;97,2%); Dipirona (68;94,4%); Sinvastatina (43;59,72%); Enoxaparina (42;58,33%); Amiodarona (29;40,27%); Sertralina (28;38,88%); Espironolactona (21;29,16%); e Atenolol (11;15,27%), cujas interações poderiam potencializar ou inibir a ação anticoagulante. Das interações, 14 (58,33%) eram de gravidade moderada, 10 (41,66%) maior e 14 (58,33%) de efeito rápido. Conclusão: A polifarmácia e o uso de anticoagulante oral em idosos cardiopatas é comum e, conhecer as interações medicamentosas, é imperativa, considerando que potencializam ou diminuem a ação anticoagulante, com gravidade maior ou moderada


Objetivo: Relacionar las interacciones medicamentosas de los anticoagulantes orales con los medicamentos utilizados por ancianos internados em um hospital cardiológico. Método:Estudio exploratorio, prospectivo, con 16 ancianos en uso de anticoagulantes orales, internados en una institución cardiológica gubernamental de São Paulo entre noviembre y diciembre de 2017. Resultados:Entre 73 medicamentos prescritos y analizados en el Micromedex 2.0, 24 (33,3%) interactuaban con la Varfarina, único anticoagulante oral prescrito. Se encontró Omeprazol (70, 97,2%); Dipirona (68, 94,4%); Sinvastatina (43, 59,72%); Enoxaparina (42, 58,33%); Amiodarona (29, 40,27%); Sertralina (28, 38,88%); Espironolactona (21, 29,16%); y Atenolol (11, 15,27%), cuyas interacciones podrían potenciar o inhibir la acción anticoagulante. De las interacciones, 14 (58,33%) eran de gravedad moderada, 10 (41,66%) mayor y 14 (58,33%) de efecto rápido. Conclusión: La polifarmacia y el uso de anticoagulante oral en ancianos cardiopatas es común y, conocer las interacciones medicamentosas, es imperativa, considerando que potencian o disminuyen la acción anticoagulante, con gravedad mayor o moderada


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Varfarina/uso terapêutico , Interações de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Anticoagulantes/uso terapêutico , Varfarina/efeitos adversos , Saúde do Idoso , Anticoagulantes/efeitos adversos
18.
Gastroenterol. hepatol. (Ed. impr.) ; 42(8): 465-475, oct. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183882

RESUMO

Objetivo: Determinar la comorbilidad y las potenciales interacciones-farmacológicas (IFs) entre los antivirales de acción-directa pangenotípicos (AADp) y la medicación-concomitante asociada a los pacientes con hepatitis C crónica (HCC) en práctica clínica habitual en España. Métodos: Diseño observacional retrospectivo. Se incluyeron pacientes ≥18 años con diagnóstico de HCC, en tratamiento antiviral y visitados durante el año 2017. Se diferenciaron 2 grupos en función de la edad (<50 y ≥50 años). Las variables recogidas fueron: edad, género, comorbilidad general/específica, medicación-concomitante y potenciales IFs (www.hep-druginteractions.org). Los AADp analizados fueron: a) sofosbuvir/velpatasvir (SOF/VEL); b) glecaprevir/pibrentasvir; y c) sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Análisis-estadístico bivariante: p<0,05. Resultados: Se reclutaron 3.430 pacientes, edad-media de 56,9 años y el 60,3% varones. El promedio del índice Charlson fue 0,8 puntos. Distribución por rangos de edad: 18-49 (28,9%) y ≥50 años (71,1%). El promedio de medicamentos fue: 3,1 (DE: 2,6) por paciente. El porcentaje total de potenciales IFs fue: 8,6% débil, 40,5% clínicamente significativas y 10,0% medicación contraindicada. Estas interacciones fueron mayores en los pacientes ≥50 años (8,6%; 43,8% y 12,4%, respectivamente, p<0,001). Para todas las edades SOF/VEL en comparación con glecaprevir/pibrentasvir y SOF/VEL/VOX presentó un menor porcentaje de interacciones-débiles (1,3% vs. 6,6% y 5,9%, p<0,001); interacciones clínicamente-significativas (53,4%, vs. 77,4% y 66,3%, p<0,001) y medicación-contraindicada (1,7% vs. 8,3% y 10,7%, p<0,001). Conclusiones: Los sujetos con HCC presentan una elevada comorbilidad y consumo de medicación concomitante, especialmente en pacientes mayores, circunstancia que repercute en una mayor exposición a potenciales IFs. Aunque la tasa de IFs fue considerable con las 3 combinaciones analizadas, SOF/VEL mostró una menor proporción clínicamente relevante


Objective: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain. Methods: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05. Results: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively. Conclusions: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Antivirais , Comorbidade , Interações de Medicamentos , Espanha/epidemiologia , Estudos Retrospectivos , Análise Estatística , Estudos Longitudinais
19.
Life Sci ; 235: 116818, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473193

RESUMO

AIMS: Considering the potential oral administration sequences and role of microbiota for metformin (MET) and berberine (BBR) during anti-diabetic treatments, the current study aimed to investigate the pharmacokinetic interactions between MET and BBR in rats after oral administration at different sequences and impacts of microbiota on such interactions. MAIN METHODS: Sprague-Dawley rats were divided into five groups as per what was orally administered to them: MET (G1)/BBR (G2) at 200 mg/kg, BBR 2-hour (h) after dosing MET (G3), MET 2-h after dosing BBR (G4) or MET with BBR at the same time (G5) followed by monitoring their pharmacokinetic profiles. Further in vitro incubations mimicking the above five treatments in rat intestinal content (G1R-G5R), human fecalase (G1H-G5H) and selected bacteria (G1B-G5B) were conducted for both MET and BBR (10 µg/ml for G1R/H-G5R/H and 50 µM for G1B-G5B) up to 24-h. Concentrations of MET and BBR were analyzed by LC/MS/MS. KEY FINDINGS: Although BBR was barely measurable in vivo, it significantly increased systemic exposure of MET in G3/G4. Consistent with pharmacokinetic findings, sequential in vitro incubations of MET and BBR in both rat intestinal content and human fecalase demonstrated significant increase on MET persisted after 24-h incubation in G3R/H & G4R/H. Moreover, post-dose (G3B) and pre-dose (G4B) of BBR decreased the MET degradation significantly in most selected bacteria. SIGNIFICANCE: Our finding for the first time demonstrated the significant effect of sequential co-administration of BBR and MET on their pharmacokinetic interactions, which could be related to their microbiota mediated metabolisms in gastrointestinal tract (GI).


Assuntos
Bactérias/efeitos dos fármacos , Berberina/farmacocinética , Interações de Medicamentos , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacocinética , Metformina/farmacocinética , Administração Oral , Animais , Berberina/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Esquema de Medicação , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
20.
Medicine (Baltimore) ; 98(37): e17101, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517840

RESUMO

BACKGROUND: Caregivers encounter serious and substantial challenges in managing hypertension in patients with subclinical or clinical borderline personality disorder (BPD). These challenges include therapeutic conflicts resulting from harmful drug-drug, and drug-disease interactions. Current guidelines provide no recommendations for concurrent psychotropic and antihypertensive treatment of hypertensive BPD patients who are at even greater cardiovascular risk. METHODS: We conducted a systematic literature review to assess the extent of available evidence on prevalence rates, cardiovascular risk factors, therapeutic conflicts, and evidence-based treatment recommendations for patients with co-occurring hypertension and BPD. Search terms were combined for hypertension and BPD in PubMed, MEDLINE, EMBASE, Cochrane, and PsycINFO databases. RESULTS: We included 11 articles for full-text evaluation and found a very high prevalence of hypertension and substantial cardiovascular risk in studies on co-occurring BPD and hypertension. However, we identified neither studies on harmful drug-drug and drug-disease interactions nor studies with treatment recommendations for co-occurring hypertension and BPD. CONCLUSIONS: Increased prevalence of hypertension in BPD patients, and therapeutic conflicts of psychotropic agents strongly suggest careful evaluation of treatment strategies in this patient group. However, no studies or guidelines recommend specific therapies or strategies to resolve therapeutic conflicts in patients with hypertension and BPD. This evidence gap needs attention in this population at high risk for cardiovascular disease.


Assuntos
Transtorno da Personalidade Borderline/complicações , Hipertensão/tratamento farmacológico , Psicotrópicos/efeitos adversos , Transtorno da Personalidade Borderline/tratamento farmacológico , Transtorno da Personalidade Borderline/psicologia , Interações de Medicamentos , Humanos , Hipertensão/psicologia , Prevalência , Psicotrópicos/uso terapêutico
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