Publications by authors named "Nylen H"

Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD.Treatment-naïve Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART.

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Previous in vitro studies have shown that microRNA-27b (miR-27b) may regulate mRNA levels of CYP3A4, vitamin D receptor (VDR), and Peroxisome proliferator-activated receptor α (PPAR α) as well as CYP3A4 protein expression and activity. In vitro studies have also shown that vitamin D may affect the expression of CYP3A4. The primary aim of this pilot study was to investigate the association between miR-27b and CYP3A expression and activity.

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The endogenous oxysterol 4β-hydroxycholesterol may be used as a marker for the drug-metabolizing enzymes cytochrome P450 3A (CYP3A). The primary aim of this study was to investigate the effect of statin treatment on plasma 4β-hydroxycholesterol concentrations. Plasma samples from a previously performed clinical study where gallstone patients had been treated with placebo (n = 6), 20 mg fluvastatin (n = 9) or 80 mg atorvastatin (n = 9) daily for 4 weeks were analysed.

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In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25-hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25-hydroxyvitamin D3 were analysed in samples from three previously performed studies, and the correlation between these levels and suggested in vivo markers of CYP3A activity was investigated by means of nonparametric correlation.

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When developing new drugs appropriate markers for detecting induction and inhibition of cytochrome P450 3A enzymes (CYP3A) are needed. The aim of the present study was to evaluate the quinine/3-hydroxyquinine metabolic ratio (quinine MR) with other suggested markers for CYP3A induction: endogenously formed 4β-hydroxycholesterol, midazolam clearance in plasma and the 6β-hydroxycortisol/cortisol ratio in urine. We have previously performed a clinical trial in which 24 healthy subjects were randomized to take 10, 20 or 100 mg daily doses of rifampicin for 14 days (n = 8 in each group) to achieve a low and moderate CYP3A induction.

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CYP3A4, considered the most important enzyme in drug metabolism, is often involved in drug-drug interactions. When developing new drugs, appropriate markers for detecting CYP3A4 induction are needed. Our study compared endogenously formed 4β-hydroxycholesterol with the midazolam clearance in plasma and the 6β-hydroxycortisol/cortisol ratio in urine as markers for CYP3A4 induction.

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The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolizing CYP3A enzymes. In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated. Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomized to either placebo or high-dose (4000 IU/day) vitamin D for 12 months.

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Aim: To compare plasma 4β-hydroxycholesterol : cholesterol with urinary 6β-hydroxycortisol : cortisol as markers of cytochrome P4503A4 activity before and after treatment with rifampicin for 2 weeks.

Method: 6β-hydroxycortisol and cortisol were determined by liquid chromatography tandem mass spectrometry and 4β-hydroxycholesterol was determined by gas chromatography-mass spectrometry in three groups of healthy volunteers.

Results: Induction ratios for 6β-hydroxycortisol : cortisol were 1.

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We investigated the effects of pharmacogenetic variations and efavirenz pharmacokinetics on inter-individual differences in the extent of CYP3A induction by efavirenz using 4β-hydroxycholesterol/cholesterol (4β-OHC/Chol) as a marker for CYP3A induction. Plasma 4β-hydroxycholesterol and cholesterol concentrations were determined at baseline, and at the 4th, 16th and 48th week of efavirenz-based highly active antiretroviral therapy in antiretroviral therapy-naive HIV patients (n=77). Efavirenz plasma concentrations were quantified at weeks 4 and 16.

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Purpose: The purpose of this study was to determine the 4β-hydroxycholesterol to cholesterol ratio in mothers and neonates at the time of birth and 4 months post-partum.

Method: 21 mothers and 22 neonates were recruited at the delivery ward at Karolinska University Hospital, Huddinge, Sweden. Blood samples taken from mothers and neonates at birth and 4 months post-partum were analysed for 4β-hydroxycholesterol and cholesterol.

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We have proposed that 4β-hydroxycholesterol (4β-OHC) may be used as an endogenous marker of CYP3A activity. The cholesterol metabolite 4β-OHC is formed by CYP3A4. Treatment of patients with strong inducers of CYP3A enzymes, e.

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