ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2009
Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo.
Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 57 citations in OpenAlex.
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- A Promising Approach to Treat Psoriasis: Inhibiting Cytochrome P450 3A4 Metabolism to Enhance Desoximetasone Therapy.Pharmaceutics · 2023Article
- Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-Acta pharmaceutica Sinica. B · 2022Article
- A Critical Overview of the Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption.The AAPS journal · 2022Review
- The Promise of Nanotechnology in Personalized Medicine.Journal of personalized medicine · 2022Review
- Nanoparticulate Drug Delivery Strategies to Address Intestinal Cytochrome P450 CYP3A4 Metabolism towards Personalized Medicine.Pharmaceutics · 2021Review
- Three-dimensional aspects of formulation excipients in drug discovery: a critical assessment on orphan excipients, matrix effects and drug interactions.Journal of pharmaceutical analysis · 2020Review
- The Impact of Surfactant Composition and Surface Charge of Niosomes on the Oral Absorption of Repaglinide as a BCS II Model Drug.International journal of nanomedicine · 2020Article
- Safety and Biopharmaceutical Challenges of Excipients in Off-Label Pediatric Formulations.International journal of general medicine · 2020Review
- Regulations of Xenobiotics and Endobiotics on Carboxylesterases: A Comprehensive Review.European journal of drug metabolism and pharmacokinetics · 2016Review
- The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters-an Update.The AAPS journal · 2016Article
- Scientific Opinion on the re-evaluation of polyoxyethylene sorbitan monolaurate (E 432), polyoxyethylene sorbitan monooleate (E 433), polyoxyethylene sorbitan monopalmitate (E 434), polyoxyethylene sorbitan monostearate (E 435) and polyoxyethylene sorbitan tristearate (E 436) as food additives.EFSA journal. European Food Safety Authority · 2015Article
- Commonly used excipients modulate UDP-glucuronosyltransferase 2b7 activity to improve nalbuphine oral bioavailability in humans.Pharmaceutical research · 2014Article
- In vitro evaluation of the inhibitory potential of pharmaceutical excipients on human carboxylesterase 1A and 2.PloS one · 2014Article
- Improved oral bioavailability of BCS class 2 compounds by self nano-emulsifying drug delivery systems (SNEDDS): the underlying mechanisms for amiodarone and talinolol.Pharmaceutical research · 2013Article
- Enhanced Permeability of Etoposide across Everted Sacs of Rat Small Intestine by Vitamin E-TPGS.Iranian journal of pharmaceutical research : IJPR · 2013Article
- Impact of excipient interactions on drug bioavailability from solid dosage forms.Pharmaceutical research · 2012Review
- Evaluation of surfactants as solubilizing agents in microsomal metabolism reactions with lipophilic substrates.In vitro cellular & developmental biology. Animal · 2011Article
- Inhibitive effect of cremophor RH40 or tween 80-based self-microemulsiflying drug delivery system on cytochrome P450 3A enzymes in murine hepatocytes.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2010Article
- Absorption enhancement of adefovir dipivoxil by incorporating MCT and ethyl oleate complex oil phase in emulsion.Acta pharmacologica Sinica · 2010Article
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8 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Nonionic surfactants are commonly used as excipients in pharmaceutical formulation, but recent studies demonstrate that the ingredients affect the pharmacokinetics of the active drugs. However, the mechanisms are largely unknown. Here, we examined the effects of four common nonionic surfactants polysorbate 20, polyoxyl 35 castor oil, polyoxyl 40 stearate and poloxamer 188, on cytochrome P450 3A in vitro and in vivo using midazolam as a probe. We first examined the effects of these surfactants on the 1'-hydroxylation of midazolam in isolated rat liver and intestinal microsomes. All the surfactants tested inhibited midazolam 1'-hydroxylation in a concentration-dependent manner and presented a mixed competitive inhibitory model with decreased V(max) and increased K(m) values in vitro. Among the tested nonionic surfactants, polysorbate 20 was the most potent inhibitor of midazolam 1'-hydroxylation with an IC(50) of 2.06 and 0.39mgml(-1) in the liver and intestinal microsomes, respectively. These surfactants were also tested in vivo as we investigated their effects on the pharmacokinetics of midazolam in rats. These four surfactants displayed different inhibitory patterns in terms of the AUC of midazolam and 1'-hydroxymidazolam. Polysorbate 20 significantly increased both AUC(0-4h) and AUC(0-infinity) of midazolam and decreased the AUC(0-4h) of 1'-hydroxymidazolam to about 40% (p<0.05) in both single- and multiple-treated rats, along with a significant decrease of the metabolic ratio of 1'-hydroxymidazolam/midazolam to 25%. Polyoxyl 35 castor oil, polyoxyl 40 stearate and poloxamer 188 displayed complicated inhibition on the 1'-hydroxylation of midazolam dependent on the administration formula. These results confirmed that effects of these surfactants would have potential inhibitory effects on cytochrome P450 3A and altered midazolam bioavailability. Therefore, caution is needed when selecting nonionic surfactants in drug formulation.
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