Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
Aged
Aged, 80 and over
Alleles
Antidiuretic Hormone Receptor Antagonists
/ pharmacokinetics
Cholesterol
/ blood
Cytochrome P-450 CYP3A
/ genetics
Female
Genotype
Heart Failure
/ drug therapy
Humans
Hydroxycholesterols
/ blood
Male
Sodium
/ blood
Tolvaptan
/ pharmacokinetics
Vitamin D
/ analogs & derivatives
4β-hydroxycholesterol
ABCB1
CYP3A5
pharmacokinetics
tolvaptan
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
05
08
2019
accepted:
21
10
2019
pubmed:
28
10
2019
medline:
18
12
2020
entrez:
26
10
2019
Statut:
ppublish
Résumé
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.
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Antidiuretic Hormone Receptor Antagonists
0
Hydroxycholesterols
0
Vitamin D
1406-16-2
cholest-5-ene-3,4-diol
17320-10-4
Tolvaptan
21G72T1950
Cholesterol
97C5T2UQ7J
Sodium
9NEZ333N27
25-hydroxyvitamin D
A288AR3C9H
CYP3A5 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-363Informations de copyright
© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Références
Fukunami M, Matsuzaki M, Hori M, Izumi M. Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study. Cardiovasc Drugs Ther. 2011;25:47-56.
Shoaf SE, Bricmont P, Mallikaarjun S. Absolute bioavailability of tolvaptan and determination of minimally effective concentrations in healthy subjects. Int J Clin Pharmacol Ther. 2012;50:150-156.
Inomata T, Izumi T, Matsuzaki M, Hori M, Hirayama A. Phase III clinical pharmacology study of tolvaptan. Cardiovasc Drugs Ther. 2011;25:57-65.
U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA limits duration and usage of Samsca (tolvaptan) due to possible liver injury leading to organ transplant or death. 2013. https://www.fda.gov/Drugs/DrugSafety/ucm350062.htm. Accessed July 30, 2019.
Hirai K, Shimomura T, Moriwaki H, et al. Risk factors for hypernatremia in patients with short- and long-term tolvaptan treatment. Eur J Clin Pharmacol. 2016;72:1177-1183.
Shoaf SE, Wang Z, Bricmont P, Mallikaarjun S. Pharmacokinetics, pharmacodynamics, and safety of tolvaptan, a nonpeptide AVP antagonist, during ascending single-dose studies in healthy subjects. J Clin Pharmacol. 2007;47:1498-1507.
Mazzarino M, Buccilli V, de la Torre X, et al. Characterization of the phase I and phase II metabolic profile of tolvaptan by in vitro studies and liquid chromatography-mass spectrometry profiling: relevance to doping control analysis. J Pharm Biomed Anal. 2017;145:555-568.
Australian Government Department of Health and Ageing. Australian Public Assessment Report for Tolvaptan. 2012. https://www.tga.gov.au/sites/default/files/auspar-tolvaptan-121004.pdf. Accessed July 30, 2019.
Slizgi JR, Lu Y, Brouwer KR, et al. Inhibition of human hepatic bile acid transporters by tolvaptan and metabolites: contributing factors to drug-induced liver injury? Toxicol Sci. 2015;149:237-250.
Shoaf SE, Ohzone Y, Ninomiya S-I, et al. In vitro P-glycoprotein interactions and steady-state pharmacokinetic interactions between tolvaptan and digoxin in healthy subjects. J Clin Pharmacol. 2011;51:761-769.
Xie HG, Wood AJ, Kim RB, Stein CM, Wilkinson GR. Genetic variability in CYP3A5 and its possible consequences. Pharmacogenomics. 2004;5:243-272.
Hattori Y, Tanaka H, Teranishi J, et al. Influence of cytochrome P450 3A5 polymorphisms on viral infection incidence in kidney transplant patients treated with tacrolimus. Transplant Proc. 2014;46:570-573.
Ishida T, Naito T, Sato H, Kawakami J. Relationship between the plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in patients with cancer pain. Drug Metab Pharmacokinet. 2016;31:242-248.
Hodges LM, Markova SM, Chinn LW, et al. Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenet Genomics. 2011;21:152-161.
Naito T, Mino Y, Aoki Y, et al. ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affect renal function in patients with rheumatoid arthritis. Clin Chim Acta. 2015;445:79-84.
Kurata Y, Ieiri I, Kimura M, et al. Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin Pharmacol Ther. 2002;72:209-219.
Mao J, Martin I, McLeod J, et al. Perspective: 4β-hydroxycholesterol as an emerging endogenous biomarker of hepatic CYP3A. Drug Metab Rev. 2017;49:18-34.
Diczfalusy U, Nylén H, Elander P, Bertilsson L. 4β-hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans. Br J Clin Pharmacol. 2011;71:183-189.
Thummel KE, Brimer C, Yasuda K, et al. Transcriptional control of intestinal cytochrome P-4503A by 1α,25-dihydroxy vitamin D3. Mol Pharmacol. 2001;60:1399-1406.
Tveden-Nyborg P, Bergmann TK, Lykkesfeldt J. Basic & Clinical Pharmacology & Toxicology policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol. 2018;123:233-235.
Flockhart DA. Drug Interactions: Cytochrome P450 Drug interaction Table. Indiana University School of Medicine. 2007. https://drug-interactions.medicine.iu.edu. Accessed July 30, 2019.
Hoshikawa K, Naito T, Saotome M, Maekawa Y, Kawakami J. Validated liquid chromatography coupled to tandem mass spectrometry method for simultaneous quantitation of tolvaptan and its five major metabolites in human plasma. Ann Clin Biochem. 2019;56:387-396.
Naito T, Kubono N, Ishida T, et al. CYP3A activity based on plasma 4β-hydroxycholesterol during the early postpartum period has an effect on the plasma disposition of amlodipine. Drug Metab Pharmacokinet. 2015;30:419-424.
Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247-254.
Du Bois D. A formula to estimate the approximate surface area if height and weight be known. Nutrition. 1989;5:303-311.
Shoaf SE, Mallikaarjun S, Bricmont P. Effect of grapefruit juice on the pharmacokinetics of tolvaptan, a non-peptide arginine vasopressin antagonist, in healthy subjects. Eur J Clin Pharmacol. 2012;68:207-211.
Suzuki Y, Muraya N, Fujioka T, et al. Factors involved in phenoconversion of CYP3A using 4β-hydroxycholesterol in stable kidney transplant recipients. Pharmacol Rep. 2019;71:276-281.
Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317-322.
Lindh JD, Andersson ML, Eliasson E, Björkhem-Bergman L. Seasonal variation in blood drug concentrations and a potential relationship to vitamin D. Drug Metab Dispos. 2011;39:933-937.
Naito T, Ohshiro J, Sato H, et al. Relationships between concomitant biologic DMARDs and prednisolone administration and blood tacrolimus exposure or serum CYP3A4/5-related markers in rheumatoid arthritis patients. Clin Biochem. 2019;69:8-14.
Wang C, Xiong B, Cai L. Effects of tolvaptan in patients with acute heart failure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2017;17:164-174.
Keppler D. The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia. Drug Metab Dispos. 2014;42:561-565.
Kawamoto R, Ninomiya D, Hasegawa Y, et al. Association between serum bilirubin and estimated glomerular filtration rate among elderly persons. PLoS ONE. 2014;9:e115294.
Sakoh T, Nakayama M, Tanaka S, et al. Association of serum total bilirubin with renal outcome in Japanese patients with stages 3-5 chronic kidney disease. Metabolism. 2015;64:1096-1102.
Pilz S, Iodice S, Zittermann A, Grant WB, Gandini S. Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis. 2011;58:374-382.
Jhee JH, Nam KH, An SY, et al. Severe vitamin D deficiency is a risk factor for renal hyperfiltration. Am J Clin Nutr. 2018;108:1342-1351.
Albarmawi A, Czock D, Gauss A, et al. CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores. Br J Clin Pharmacol. 2014;77:160-169.
Neuhoff S, Tucker GT. Was 4β-hydroxycholesterol ever going to be a useful marker of CYP3A4 activity? Br J Clin Pharmacol. 2018;84:1620-1621.
Gravel S, Chiasson JL, Gaudette F, Turgeon J, Michaud V. Use of 4β-hydroxycholesterol plasma concentrations as an endogenous biomarker of CYP3A activity: clinical validation in individuals with type 2 diabetes. Clin Pharmacol Ther. 2019;106:831-840.