Mikko Neuvonen
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View article: Effects of nonsense genetic variants on OATP1B1 expression and transport activity in vitro
Effects of nonsense genetic variants on OATP1B1 expression and transport activity in vitro Open
Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) is an influx transporter expressed in the basolateral membrane of hepatocytes, playing a key role in the hepatic uptake and clearance of various drugs and endogenous …
View article: Systemic N‐Acylethanolamines and Other Lipid Mediators Are Associated With <scp>NSAID</scp>‐Exacerbated Respiratory Disease
Systemic N‐Acylethanolamines and Other Lipid Mediators Are Associated With <span>NSAID</span>‐Exacerbated Respiratory Disease Open
View article: Comparative uptake of statins by hepatic organic anion transporting polypeptides
Comparative uptake of statins by hepatic organic anion transporting polypeptides Open
Uptake into hepatocytes by the organic anion transporting polypeptides (OATP) 1B1, 1B3, and 2B1 can form a rate-determining step in drug clearance. While several lipid-lowering statin drugs are substrates of the hepatic OATPs, the literatu…
View article: Transport of statins by multidrug resistance-associated proteins 1 and 5
Transport of statins by multidrug resistance-associated proteins 1 and 5 Open
Statins are widely used in the treatment of hypercholesterolemia but also associated with muscle-related adverse effects. Multidrug resistance-associated protein (MRP) 1 and 5 are expressed in the skeletal muscle, where they may regulate i…
View article: Identification of Genetic Variants Associated with Pravastatin and Pitavastatin Pharmacokinetics
Identification of Genetic Variants Associated with Pravastatin and Pitavastatin Pharmacokinetics Open
A clinical trial was carried out to investigate the pharmacogenetics of single‐dose pravastatin and pitavastatin pharmacokinetics in 173 and 164 healthy participants. Additionally, 96 participants were included from previous pharmacogeneti…
View article: Genetic and Functional Characterization of <i>DPYD</i> Exon 4 Deletion Common in the Finnish Population
Genetic and Functional Characterization of <i>DPYD</i> Exon 4 Deletion Common in the Finnish Population Open
View article: A Phenotyping Tool for Seven Cytochrome P450 Enzymes and Two Transporters: Application to Examine the Effects of Clopidogrel and Gemfibrozil
A Phenotyping Tool for Seven Cytochrome P450 Enzymes and Two Transporters: Application to Examine the Effects of Clopidogrel and Gemfibrozil Open
Clinical cocktails for cytochrome P450 (CYP) phenotyping lack a marker for CYP2C8. We aimed to combine the CYP2C8 index drug repaglinide with the Geneva cocktail (caffeine/CYP1A2, bupropion/CYP2B6, flurbiprofen/CYP2C9, omeprazole/CYP2C19, …
View article: Accumulation of altered serum bile acids predicts liver injury after portoenterostomy in biliary atresia
Accumulation of altered serum bile acids predicts liver injury after portoenterostomy in biliary atresia Open
Biliary atresia, a fibro-obliterating biliary disease of infants, remains the most common indication for pediatric liver transplantation because of the rapid progression of liver injury. To identify predictive biomarkers of disease progres…
View article: Candesartan Has No Clinically Meaningful Effect on the Plasma Concentrations of Cytochrome P450 2C8 Substrate Repaglinide in Humans
Candesartan Has No Clinically Meaningful Effect on the Plasma Concentrations of Cytochrome P450 2C8 Substrate Repaglinide in Humans Open
View article: Population Pharmacokinetic Quantification of CYP2D6 Activity in Codeine Metabolism in Ambulatory Surgical Patients for Model-Informed Precision Dosing
Population Pharmacokinetic Quantification of CYP2D6 Activity in Codeine Metabolism in Ambulatory Surgical Patients for Model-Informed Precision Dosing Open
Our final model leads the way in implementing model-informed precision dosing in codeine therapy and identifies the use of genetic testing as an integral component in the effort to implement rational pharmacotherapy with codeine.
View article: In vitro assessment of inhibitory effects of kinase inhibitors on CYP2C9, 3A and 1A2: Prediction of drug-drug interaction risk with warfarin and direct oral anticoagulants
In vitro assessment of inhibitory effects of kinase inhibitors on CYP2C9, 3A and 1A2: Prediction of drug-drug interaction risk with warfarin and direct oral anticoagulants Open
Our results suggest that several kinase inhibitors, including vatalanib and linsitinib, can cause CYP-mediated drug-drug interactions with warfarin and, to a lesser extent, with apixaban and rivaroxaban. The work provides mechanistic insig…
View article: Ticagrelor modestly raises plasma riboflavin concentration in humans and inhibits riboflavin transport by BCRP and MRP4
Ticagrelor modestly raises plasma riboflavin concentration in humans and inhibits riboflavin transport by BCRP and MRP4 Open
Riboflavin (vitamin B 2 ) has been proposed as a biomarker for breast cancer resistance protein (BCRP) activity. In recent studies in mice, cynomolgus monkeys, and humans, BCRP‐inhibiting drugs increased the plasma concentration of ribofla…
View article: Genome‐Wide Association Study of Atorvastatin Pharmacokinetics: Associations With <i>SLCO1B1</i>, <i>UGT1A3</i>, and <i>LPP</i>
Genome‐Wide Association Study of Atorvastatin Pharmacokinetics: Associations With <i>SLCO1B1</i>, <i>UGT1A3</i>, and <i>LPP</i> Open
In a genome‐wide association study of atorvastatin pharmacokinetics in 158 healthy volunteers, the SLCO1B1 c.521T>C (rs4149056) variant associated with increased area under the plasma concentration‐time curve from time zero to infinity (AU…
View article: Non‐targeted metabolomics for the identification of plasma metabolites associated with organic anion transporting polypeptide <scp>1B1</scp> function
Non‐targeted metabolomics for the identification of plasma metabolites associated with organic anion transporting polypeptide <span>1B1</span> function Open
Our aim was to evaluate biomarkers for organic anion transporting polypeptide 1B1 (OATP1B1) function using a hypothesis‐free metabolomics approach. We analyzed fasting plasma samples from 356 healthy volunteers using non‐targeted metabolit…
View article: Screening of 16 major drug glucuronides for time-dependent inhibition of nine drug-metabolizing CYP enzymes – detailed studies on CYP3A inhibitors
Screening of 16 major drug glucuronides for time-dependent inhibition of nine drug-metabolizing CYP enzymes – detailed studies on CYP3A inhibitors Open
Time-dependent inhibition of cytochrome P450 (CYP) enzymes has been observed for a few glucuronide metabolites of clinically used drugs. Here, we investigated the inhibitory potential of 16 glucuronide metabolites towards nine major CYP en…
View article: Solanidine is a sensitive and specific dietary biomarker for CYP2D6 activity
Solanidine is a sensitive and specific dietary biomarker for CYP2D6 activity Open
Background Individual assessment of CYP enzyme activities can be challenging. Recently, the potato alkaloid solanidine was suggested as a biomarker for CYP2D6 activity. Here, we aimed to characterize the sensitivity and specificity of sola…
View article: Protein Phosphatase 1 Regulatory Subunit 3 Beta rs4240624 Genotype Is Associated With Gallstones and With Significant Changes in Bile Lipidome
Protein Phosphatase 1 Regulatory Subunit 3 Beta rs4240624 Genotype Is Associated With Gallstones and With Significant Changes in Bile Lipidome Open
View article: Posaconazole‐ibrutinib interaction cannot be avoided by staggered dosing: How to optimize ibrutinib dose during posaconazole treatment
Posaconazole‐ibrutinib interaction cannot be avoided by staggered dosing: How to optimize ibrutinib dose during posaconazole treatment Open
Aims Ibrutinib is used in the treatment of certain B‐cell malignancies. Due to its CYP3A4‐mediated metabolism and highly variable pharmacokinetics, it is prone to potentially harmful drug‐drug interactions. Methods In a randomized, placebo…
View article: Inhibition of efflux transporters by poly ADP‐ribose polymerase inhibitors
Inhibition of efflux transporters by poly ADP‐ribose polymerase inhibitors Open
Poly ADP‐ribose polymerase (PARP) inhibitors have been approved for the treatment of various cancers. They share a similar mechanism of action but have differences in pharmacokinetic characteristics and potential for drug–drug interactions…
View article: The effect of hydroxychloroquine on cholesterol metabolism in statin treated patients after myocardial infarction
The effect of hydroxychloroquine on cholesterol metabolism in statin treated patients after myocardial infarction Open
Combined with a high-dose statin, hydroxychloroquine had no additional effect on serum cholesterol concentration or cholesterol absorption. However, the findings suggest that hydroxychloroquine interferes with lanosterol synthesis, and the…
View article: Extraesophageal reflux and reflux aspiration in dogs with respiratory diseases and in healthy dogs
Extraesophageal reflux and reflux aspiration in dogs with respiratory diseases and in healthy dogs Open
Background Salivary bile acids are used to diagnose extraesophageal reflux (EER) and to evaluate the risk of reflux aspiration that is associated with respiratory diseases in dogs. Objectives To study total bile acid (TBA) concentrations i…
View article: Novel inhibitors of breast cancer resistance protein (BCRP, ABCG2) among marketed drugs
Novel inhibitors of breast cancer resistance protein (BCRP, ABCG2) among marketed drugs Open
Drug-drug interactions (DDIs) are a major concern for the safe use of medications. Breast cancer resistance protein (BCRP) is a clinically relevant ATP-binding cassette (ABC) transporter for drug disposition. Inhibition of BCRP increases t…
View article: Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry
Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry Open
View article: A comprehensive pharmacogenomic study indicates roles for <i>SLCO1B1</i>, <i>ABCG2</i> and <i>SLCO2B1</i> in rosuvastatin pharmacokinetics
A comprehensive pharmacogenomic study indicates roles for <i>SLCO1B1</i>, <i>ABCG2</i> and <i>SLCO2B1</i> in rosuvastatin pharmacokinetics Open
Aims The aim was to comprehensively investigate the effects of genetic variability on the pharmacokinetics of rosuvastatin. Methods We conducted a genome‐wide association study and candidate gene analyses of single dose rosuvastatin pharma…
View article: Functional in vitro characterization of SLCO1B1 variants and simulation of the clinical pharmacokinetic impact of impaired OATP1B1 function.
Functional in vitro characterization of SLCO1B1 variants and simulation of the clinical pharmacokinetic impact of impaired OATP1B1 function. Open
Organic Anion Transporting Polypeptide 1B1 is important to the hepatic elimination and distribution of many drugs. If OATP1B1 function is decreased, it can increase plasma exposure of e.g. several statins leading to increased risk of muscl…
View article: Genomewide Association Study of Simvastatin Pharmacokinetics
Genomewide Association Study of Simvastatin Pharmacokinetics Open
We investigated genetic determinants of single‐dose simvastatin pharmacokinetics in a prospective study of 170 subjects and a retrospective cohort of 59 healthy volunteers. In a microarray‐based genomewide association study with the prospe…
View article: Pharmacogenomics of celiprolol – evidence for a role of P‐glycoprotein and organic anion transporting polypeptide 1A2 in celiprolol pharmacokinetics
Pharmacogenomics of celiprolol – evidence for a role of P‐glycoprotein and organic anion transporting polypeptide 1A2 in celiprolol pharmacokinetics Open
The aim of this study was to search for associations of genetic variants with celiprolol pharmacokinetics in a large set of pharmacokinetic genes, and, more specifically, in a set of previously identified candidate genes ABCB1 , SLCO1A2 , …
View article: Performance of Plasma Coproporphyrin I and III as OATP1B1 Biomarkers in Humans
Performance of Plasma Coproporphyrin I and III as OATP1B1 Biomarkers in Humans Open
A previous study in 356 healthy Finnish volunteers showed that glycochenodeoxycholate 3‐O‐glucuronide (GCDCA‐3G) and glycodeoxycholate 3‐O‐glucuronide (GDCA‐3G) are promising biomarkers of organic anion transporting polypeptide 1B1 (OATP1B…
View article: Comparative Hepatic and Intestinal Efflux Transport of Statins
Comparative Hepatic and Intestinal Efflux Transport of Statins Open
Previous studies have shown that lipid-lowering statins are transported by various ATP-binding cassette (ABC) transporters. However, because of varying methods, it is difficult to compare the transport profiles of statins. Therefore, we in…
View article: Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins
Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins Open
This study aimed to comprehensively investigate the in vitro metabolism of statins. The metabolism of clinically relevant concentrations of atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, and their metaboli…