Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women

Filgueira, Gabriela Campos de Oliveira; Filgueira, Osmany Alberto Silva; Carvalho, Daniela Miarelli; Marques, Maria Paula; Moisés, Elaine Christine Dantas; Duarte, Geraldo; Lanchote, Vera Lúcia; Cavalli, Ricardo de Carvalho

doi:10.1111/bcp.13226

Cited by 18 publications

(27 citation statements)

References 48 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, pregnant women with gestational diabetes showed significantly higher C max and AUC of lidocaine following peridural anesthesia administration of lidocaine than non-diabetic patients [61]. However, oral plasma concentrations of nifedipine [62] and metoprolol [63] in pregnant women with gestational diabetes were comparable to those in non-diabetic pregnant women. Adith et al [64] investigated phenytoin kinetics in 10 male type 1 and 10 type 2 diabetic patients.…”

Section: Cyp450smentioning

confidence: 90%

Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

Yang

Liu

2020

Pharmaceutics

View full text Add to dashboard Cite

The pharmacokinetics of a drug is dependent upon the coordinate work of influx transporters, enzymes and efflux transporters (i.e., transporter-enzyme interplay). The transporter–enzyme interplay may occur in liver, kidney and intestine. The influx transporters involving drug transport are organic anion transporting polypeptides (OATPs), peptide transporters (PepTs), organic anion transporters (OATs), monocarboxylate transporters (MCTs) and organic cation transporters (OCTs). The efflux transporters are P-glycoprotein (P-gp), multidrug/toxin extrusions (MATEs), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). The enzymes related to drug metabolism are mainly cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyltransferases (UGTs). Accumulating evidence has demonstrated that diabetes alters the expression and functions of CYP450s and transporters in a different manner, disordering the transporter–enzyme interplay, in turn affecting the pharmacokinetics of some drugs. We aimed to focus on (1) the imbalance of transporter-CYP450 interplay in the liver, intestine and kidney due to altered expressions of influx transporters (OATPs, OCTs, OATs, PepTs and MCT6), efflux transporters (P-gp, BCRP and MRP2) and CYP450s (CYP3As, CYP1A2, CYP2E1 and CYP2Cs) under diabetic status; (2) the net contributions of these alterations in the expression and functions of transporters and CYP450s to drug disposition, therapeutic efficacy and drug toxicity; (3) application of a physiologically-based pharmacokinetic model in transporter–enzyme interplay.

show abstract

Section: Cyp450smentioning

confidence: 90%

Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

Yang

Liu

2020

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…During the past several years, intense investigative and clinical efforts have focused on the impact of drug‐altered pharmacokinetics in diabetes [9]. Diabetes mellitus can alter the kinetic disposition and the metabolism of drugs on the investigated drug, and on its metabolic and excretion pathways [10–12]. Recently, some papers reported that the pharmacokinetics of clinical drugs is altered in individuals with diabetes mellitus, including gentamicin [13], metoprolol [14], berberine [15], baicalin [16], catalpol [17], and geniposide [18].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, some papers reported that the pharmacokinetics of clinical drugs is altered in individuals with diabetes mellitus, including gentamicin [13], metoprolol [14], berberine [15], baicalin [16], catalpol [17], and geniposide [18]. Specifically, type 2 diabetes mellitus alters the pharmacokinetic (PK) features of some drugs such as amlodipine, nisoldipine, and nifedipine [9, 12, 19]. The curative effects of some TCMs can be reflected when the body is in a specific pathological state.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC‐MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats

Wang

Xie

et al. 2021

J of Separation Science

View full text Add to dashboard Cite

Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple‐reaction‐monitoring mode with an electrospray positive‐ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single‐dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.

show abstract

“…Nifedipine, a dihydropyridin calcium channel, is mostly utilized for the clinical treatment of precordial angina, hypertension, and other vascular diseases (Yasam et al., 2016 ; Rubini et al., 2017 ). Importantly, nifedipine is a nonpolar drug that is completely absorbed by the gastrointestinal tract (Grigoriev et al., 2016 ; Filgueira et al., 2017 ). Its metabolism may be affected by microbiota in the stomach and intestine although the biotransformation of nifedipine by enteric microorganism has not yet been characterized.…”

Section: Introductionmentioning

confidence: 99%

Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine

et al. 2018

View full text Add to dashboard Cite

Nifedipine is completely absorbed by the gastrointestinal tract and its pharmacokinetics and metabolism may be influenced by microorganisms. If gut microbes are involved in the metabolism of nifedipine, plateau hypoxia may regulate the bioavailability and the therapeutic effect of nifedipine by altering the metabolic activity of the gut microbiota. We herein demonstrated for the first time that gut flora is involved in the metabolism of nifedipine by in vitro experiments. In addition, based on the results of 16S rRNA analysis of feces in rats after acute plateau, we first confirmed that the plateau environment could cause changes in the number and composition of intestinal microbes. More importantly, these changes in flora could lead to a slower metabolic activity of nifedipine in the body after an acute plateau, resulting in increased bioavailability and therapeutic efficacy of nifedipine. Our research will provide basis and new ideas for changes in the fecal flora of human acutely entering the plateau, and contribute to rational drug use of nifedipine.

show abstract

Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women

Abstract: There was no influence of T2DM on the pharmacokinetics or placental transfer of nifedipine in hypertensive women with controlled diabetes.

Cited by 18 publications

References 48 publications

Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC‐MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats

Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine

Contact Info

Product

Resources

About