CYP3A activity based on plasma 4β-hydroxycholesterol during the early postpartum period has an effect on the plasma disposition of amlodipine

Naito, Takafumi; Kubono, Naoko; Ishida, Takuya; Deguchi, Shuhei; Sugihara, Masahisa; Itoh, Hiroaki; Kanayama, Naohiro; Kawakami, Junichi

doi:10.1016/j.dmpk.2015.08.008

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…Our achievements described in the present review can be summarized as follows. 6,7,10,12,13) 1) Cachectic cancer patients exhibited high plasma concentrations of oxycodone via the decrease in CYP3A activity. The metabolic reduction in cachectic cancer patients was potentially related to the elevated serum level of IL-6.…”

Section: Resultsmentioning

confidence: 99%

“…Our research has mainly addressed the challenges of cancer pain relief in palliative care, [3][4][5][6][7][8] immunosuppressive therapy for autoimmune diseases, 9,10) antimicrobial therapy for serious conditions, 11,12) and pharmacotherapy during the perinatal period. [13][14][15] In the present review, the author describes five achievements in recent clinical research on patient factors associated with pharmacokinetics, drug efficacy, and adverse reactions as well as information on the appropriate use of pharmaceuticals. The clinical studies reviewed were conducted in accordance with the principles of the Declaration of Helsinki and its amendments and the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan.…”

Section: Introductionmentioning

confidence: 99%

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Optimization of Individual Pharmacotherapy Based on Multiple Evaluations of Patient Data

Naito

2019

Biological & Pharmaceutical Bulletin

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To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors related to the pharmacokinetics, drug efficacy, and adverse reactions observed in clinical settings. Through the clinical studies, drug information on the individual optimization of pharmacotherapy needed by health professionals including physicians and pharmacists was identified. Major findings were: 1) Cachectic cancer patients had high plasma concentrations of oxycodone via the reduction of CYP3A activity. The metabolic reduction in cachectic cancer patients was potentially related to the elevated serum level of interleukin-6. 2) Dopamine receptor D 2 (DRD2) genetic mutations and being female led to poor antiemetic efficacy of the treatment of opioid-induced nausea in prochlorperazine-treated patients. The opioid receptor μ1 (OPRM1) wild genotype in addition to being female and having high plasma concentrations of prochlorperazine increased prolactin secretion during oxycodone treatment. 3) Rheumatoid arthritis patients with a genetic mutation of ATP-binding cassette subfamily B member 1 (ABCB1) had high plasma concentrations of tacrolimus and its 13-O-demethylate. The ABCB1 genetic mutation and associated high plasma concentration of tacrolimus decreased kidney function. 4) Chronic inflammation increased the plasma voriconazole concentration via its poor metabolism, whereas it did not alter the plasma itraconazole concentration. Although co-administration of prednisolone did not affect the plasma concentration of triazole antifungals, it weakly increased voriconazole metabolism. 5) In breastfeeding women, the median milk/plasma concentration ratio of amlodipine was 0.85. However, the observed relative infant dose of amlodipine in most patients was less than 10%.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimization of Individual Pharmacotherapy Based on Multiple Evaluations of Patient Data

Naito

2019

Biological & Pharmaceutical Bulletin

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“…Saponified 4β-OHC in plasma was quantified by an LC-MS/MS method. 23 The linearity of 4β-OHC was observed at a plasma concentration range of 5-200 ng/mL (r > .999). The intra-and inter-day accuracies of 4β-OHC were 104.2%-114.5% and 94.5%-106.8%, while its intra-and inter-day imprecisions were <9.3% and 13.6%, respectively.…”

Section: Cyp3a Activitymentioning

confidence: 89%

“…Saponified 4β‐OHC in plasma was quantified by an LC‐MS/MS method . The linearity of 4β‐OHC was observed at a plasma concentration range of 5‐200 ng/mL ( r > .999).…”

Section: Methodsmentioning

confidence: 99%

Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients

Hoshikawa

Naito

Akutsu

et al. 2019

Basic Clin Pharma Tox

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Tolvaptan efficacy for heart failure has a large interindividual variation. This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients. Fifty‐eight heart failure patients receiving oral tolvaptan for volume overload were enrolled. Blood samples for determination of pre‐dose plasma concentrations of tolvaptan and its metabolites were collected. CYP3A5 and ABCB1 genotypes, plasma 4β‐hydroxycholesterol/total cholesterol ratio (4β‐OHC/TC) and 25‐hydroxyvitamin D (25‐OHD), and serum laboratory test values were evaluated. The CYP3A5*3/*3 genotype was associated with a higher plasma concentration of tolvaptan but not with its metabolic ratios. The ABCB1 3435C > T, 2677G > T/A and 1236C > T polymorphisms affected neither tolvaptan pharmacokinetics nor its metabolism. Plasma 4β‐OHC/TC and 25‐OHD concentration were not correlated with plasma tolvaptan concentration. In a stratified analysis based on CYP3A5 genotype, plasma 4β‐OHC/TC had a negative correlation with plasma tolvaptan concentration in the patients with the CYP3A5*1 allele, while the plasma concentration of 25‐OHD did not. The CYP3A5*3/*3 genotype was associated with a higher serum sodium level in the patients with volume overload. The plasma concentration of 25‐OHD had a positive correlation with the serum total bilirubin level. In conclusion, CYP3A5*3 but not ABCB1 genotypes elevated tolvaptan plasma exposure in heart failure patients. CYP3A5‐deficient patients treated with tolvaptan had a higher serum sodium level. The CYP3A5 genotype altered the relationship between plasma tolvaptan and 4β‐OHC.

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“…Several endogenous substrates of Oatps have been identified in animals or in vitro, including bile acids and their respective conjugates, bilirubin and coproporphyrin I/III (CP I/III) [17] . 4β-Hydroxycholesterol (4β-HC) [18] , [19] , [20] , [21] and 6β-hydroxycortisol (6β-HC) [22] , [23] , [24] , [25] are formed by the Cyp3a4/5-catalyzed metabolism of cholesterol and cortisol, respectively. Consequently, these compounds may be expected to the endogenous marker for Oatps and Cyp3a.…”

Section: Introductionmentioning

confidence: 99%

The utility of endogenous glycochenodeoxycholate-3-sulfate and 4β-hydroxycholesterol to evaluate the hepatic disposition of atorvastatin in rats

Yue

Xin

Wen

et al. 2021

Asian Journal of Pharmaceutical Sciences

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The liver is an important organ for drugs disposition, and thus how to accurately evaluate hepatic clearance is essential for proper drug dosing. However, there are many limitations in drug dosage adjustment based on liver function and pharmacogenomic testing. In this study, we evaluated the ability of endogenous glycochenodeoxycholate-3-sulfate (GCDCA-S) and 4β-hydroxycholesterol (4β-HC) plasma levels to evaluate organic anion-transporting polypeptide (Oatps)-mediated hepatic uptake and Cyp3a-meidated metabolism of atorvastatin (ATV) in rats. The concentration of ATV and its metabolites, 2-OH ATV and 4-OH ATV, was markedly increased after a single injection of rifampicin (RIF), an inhibitor of Oatps. Concurrently, plasma GCDCA-S levels were also elevated. After a single injection of the Cyp3a inhibitor ketoconazole (KTZ), plasma ATV concentrations were significantly increased and 2-OH ATV concentrations were decreased, consistent with the metabolism of ATV by Cyp3a. However, plasma 4β-HC was not affected by KTZ treatment despite it being a Cyp3a metabolite of cholesterol. After repeated oral administration of RIF, plasma concentrations of ATV, 2-OH ATV and 4-OH ATV were markedly increased and the hepatic uptake ratio of ATV and GCDCA-S was decreased. KTZ did not affect plasma concentrations of ATV, 2-OH ATV and 4-OH ATV, but significantly decreased the metabolic ratio of total and 4-OH ATV. However, the plasma level and hepatic metabolism of 4β-HC were not changed by KTZ. The inhibition of hepatic uptake of GCDCA-S by RIF was fully reversed after a 7-d washout of RIF. Plasma concentration and hepatic uptake ratio of GCDCA-S were correlated with the plasma level and hepatic uptake of ATV in rats with ANIT-induced liver injury, respectively. These results demonstrate that plasma GCDCA-S is a sensitive probe for the assessment of Oatps-mediated hepatic uptake of ATV. However, Cyp3a-mediated metabolism of ATV was not predicted by plasma 4β-HC levels in rats.

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CYP3A activity based on plasma 4β-hydroxycholesterol during the early postpartum period has an effect on the plasma disposition of amlodipine

Cited by 11 publications

References 37 publications

Optimization of Individual Pharmacotherapy Based on Multiple Evaluations of Patient Data

Optimization of Individual Pharmacotherapy Based on Multiple Evaluations of Patient Data

Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients

The utility of endogenous glycochenodeoxycholate-3-sulfate and 4β-hydroxycholesterol to evaluate the hepatic disposition of atorvastatin in rats

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