Drug interactions

Boobis, Alan R.; Watelet, Jean-Baptiste; Whomsley, Rhys; Benedetti, Μ. Strolin; Démoly, P.; Tipton, Keith F.

doi:10.1080/10837450902891550

Cited by 46 publications

(27 citation statements)

References 340 publications

(362 reference statements)

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“…Most of the P450s have been shown to be sensitive to induction or inhibition by several drugs (Boobis et al, 2009). The influence of inducing or inhibiting preoperative medication should therefore also be taken into account.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

et al. 2012

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To improve the modeling and simulation of pharmacokinetics in pediatric patients, research into developmental and disease-specific determinants is needed. This article describes the evaluation of the activity of in vitro cytochrome P450 (P450), an important enzyme family in drug metabolism, in children with hepatic dysfunction. The activity of six P450 isoforms (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) was evaluated in 31 patients with different pathologies, predominantly biliary atresia (n = 23). Hypervariable activity was observed for all the isoforms. Compared with average adult activity, low activity levels were seen for CYP1A2, 2C19, 2E1, and 3A4. For CYP2E1 and 3A4, a positive correlation between activity and abundance was observed. Age, comedication, and genotype could not be used as predictors for P450 activity in this patient population. In contrast, the pediatric end-stage liver disease score was negatively correlated with the ln(activity). This finding suggests a decrease in P450 activity with deteriorating hepatic function. Moreover, the activity of all isoforms was correlated, demonstrating a concomitant decrease of all isoforms in young patients with liver disease. To our knowledge, this is the first study to evaluate P450 activity in children with hepatic impairment. The presented data may provide support in the further optimization of a diseasespecific model in this patient population.

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Section: Discussionmentioning

confidence: 99%

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

et al. 2012

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“…On the other hand, PD interactions take place at the pharmacologic drug binding sites, and the consequences of the interaction may be additive, synergistic or antagonistic. 22 Drug-drug interactions (DDIs) are desirable if they reduce adverse effects or improve the efficacy of the combined agents. Conversely, they are undesirable if they hinder treatment by increasing ADRs and/or reducing treatment effectiveness.…”

Section: Drug Interactions In Elderly Peoplementioning

confidence: 99%

Inappropriate prescribing in hospitalized elderly patients

Massoud

Alagha

Taleb

2017

Int J Basic Clin Pharmacol

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Inappropriate prescribing (IP) is a major healthcare problem in elderly patients. The risk of this problem increases during hospitalization. This is due to increase morbidity and thus increases the use of medications by the inpatients. This study will clarify the problem of IP for elderly people during hospitalization and will identify the different types of it. It also will highlight some tools that are used to assess the different types of IP and the prevalence of it in elderly patients during hospitalization. Finally, the study will address the consequences of IP in the elderly inpatients and the risks associated with the use of some potentially inappropriate medications (PIMs) in the elderly.

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“…Inhibition of P450 enzymes is a major mechanism for pharmacokinetic drug interactions (Wienkers and Heath, 2005;Boobis et al, 2009). In general, P450 enzymes are inhibited either as reversible inhibition or via the more profound and prolonged irreversible or quasi-irreversible inactivation.…”

Section: Introductionmentioning

confidence: 99%

Time-Dependent Inhibition of CYP2C19 by Isoquinoline Alkaloids: In Vitro and In Silico Analysis

et al. 2015

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The cytochrome P450 2C19 (CYP2C19) enzyme plays an important role in the metabolism of many commonly used drugs. Relatively little is known about CYP2C19 inhibitors, including compounds of natural origin, which could inhibit CYP2C19, potentially causing clinically relevant metabolism-based drug interactions. We evaluated a series (N = 49) of structurally related plant isoquinoline alkaloids for their abilities to interact with CYP2C19 enzyme using in vitro and in silico methods. We examined several common active alkaloids found in herbal products such as apomorphine, berberine, noscapine, and papaverine, as well as the previously identified mechanism-based inactivators bulbocapnine, canadine, and protopine. The IC 50 values of the alkaloids ranged from 0.11 to 210 mM, and 42 of the alkaloids were confirmed to be time-dependent inhibitors of CYP2C19. Molecular docking and three-dimensional quantitative structure-activity relationship analysis revealed key interactions of the potent inhibitors with the enzyme active site. We constructed a comparative molecular field analysis model that was able to predict the inhibitory potency of a series of independent test molecules. This study revealed that many of these isoquinoline alkaloids do have the potential to cause clinically relevant drug interactions. These results highlight the need for studying more profoundly the potential interactions between drugs and herbal products. When further refined, in silico methods can be useful in the high-throughput prediction of P450 inhibitory potential of pharmaceutical compounds.

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Drug interactions

Cited by 46 publications

References 340 publications

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

Inappropriate prescribing in hospitalized elderly patients

Time-Dependent Inhibition of CYP2C19 by Isoquinoline Alkaloids: In Vitro and In Silico Analysis

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