Published May 21, 2024
| Version v1
Journal article
Open
The impact of CYP2C19 genotypes on steady-state plasma concentration of escitalopram in South Indian population with Major Depressive Disorder
Authors/Creators
- 1. SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, India
- 2. Department of Psychiatry, Sri Venkateswara Institute of Medical Sciences, Tirupati, India
Description
Background: Among depressed patients, escitalopram plasma levels differed between those who were considered as extensive metabolizers and poor metabolizers of CYP2C19. However, the majority of research utilized the dose-response relationship. Consequently, we investigated the effect of variations in the CYP2C19 gene on the levels of drug in the bloodstream of individuals suffering from Major Depressive Disorder (MDD) in south India.
Methods: A total of 109 individuals with MDD who were prescribed escitalopram at doses of 5, 10, 15, or 20 mg daily participated in this research. We used HPLC with SPD-10AVP UV-Visible detector to measure the escitalopram concentrations in the blood. The polymorphisms of the CYP2C19 were determined by employing the PCR techniques.
Results: Our study found that 55% of the subjects were intermediate metabolizers, followed by extensive (19.3%), poor (17.4%), and ultra-rapid (8.3%). The significant correlation is identified between the steady state plasma concentration and Sex with (P - Value < 0.05), insignificant correlation was seen in Age and BMI with (P - Value > 0.05). The majority of gene variants seen in the study population were CYP2C19*1/*2, accounting for 49 individuals (44.9%).
Conclusion: These findings showed that sex had a substantial impact on the CYP2C19 genetic variation. Medication administration to individuals with CYP2C19 PM requires special caution.
Files
PHAR_article_123645.pdf
Files
(287.1 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:36f8a85cadf155449d5ec6edc91954b1
|
205.2 kB | Preview Download |
|
md5:a8b6771ea4fd859289a07cfed5d9da98
|
81.9 kB | Preview Download |
Additional details
References
- Adithan C, Gerard N, Vasu S, Balakrishnan R, Shashindran CH, Krishnamoorthy R (2003) Allele and genotype frequency of CYP2C9 in Tamilnadu population. European Journal of Clinical Pharmacology 59: 707–709. https://doi.org/10.1007/s00228-003-0666-3
- Adithan C, Gerard N, Vasu S, Rosemary J, Shashindran CH, Krishnamoorthy R (2003) Allele and genotype frequency of CYP2C19 in a Tamilian population. British Journal of Clinical Pharmacology 56: 331–333. https://doi.org/10.1046/j.1365-2125.2003.01883.x
- Akasaka T, Hokimoto S, Sueta D, Tabata N, Sakamoto K, Yamamoto E (2016) Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder. American Journal of Physiology. Heart and Circulatory Physiology 310: 494–500. https://doi.org/10.1152/ajpheart.00911.2015
- American Psychiatric Association (2010) Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 5th edn. Arlington: American Psychiatric Publishing, 152 pp.
- Anichavezhi D, Shewade DG, Krishnamoorthy R, Adithan C (2010) Distribution of CYP2C19*17 allele and genotypes in an Indian population. Journal of Clinical Pharmacy and Therapeutics 37: 313–318. https://doi.org/10.1111/j.1365-2710.2011.01294.x
- Burke WJ, Gergel I, Bose A (2002) Fixed dose trial of the single isomer SSRI escitalopram in depressed outpatients. The Journal of Clinical Psychiatry 63: 331–336. https://doi.org/10.4088/JCP.v63n0410
- Diczfalusy U, Miura J, Roh HK (2008) 4b-hydroxycholesterol is a new endogenous CYP3A marker: Relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians. Pharmacogenetics and Genomics 18: 201–208. https://doi.org/10.1097/FPC.0b013e3282f50ee9
- Garnock-Jones KP, McCormack PL (2010) Escitalopram: A review of its use in the management of major depressive disorder in adults. CNS Drugs 24: 769–796. https://doi.org/10.2165/11204760-000000000-00000
- GBD (2018) Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 392: 1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7
- Goldstein JA, Ishizaki T, Chiba K, de Morais SM, Bell D, Krahn PM (1997) Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American Black populations. Pharmacogenetics 7: 59–64. https://doi.org/10.1097/00008571-199702000-00008
- Herrlin k, Massele AY, Jande M, Alm C, Tybring G, Abdi YA (1998) Bantu Tanzanians have a decreased capacity to metabolize omeprazole and mephenytoin in relation to their CYP2C19 genotype. Clinical Pharmacology & Therapeutics 4: 391–401. https://doi.org/10.1016/S0009-9236(98)90070-4
- Hicks JK, Bishop JR, Sangkuhl K, Muller DJ, Ji Y, Leckband SG (2015) Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology and Therapeutics 98: 127–134. https://doi.org/10.1002/cpt.147
- Kirino E (2012) Escitalopram for the management of major depressive disorder: A review of its efficacy, safety, and patient acceptability. Patient Preference and Adherence 6: 853–861. https://doi.org/10.2147/PPA.S22495
- Lamba JK, Dhiman RK, Kohli KK (1998) Genetic polymorphism of the hepatic cytochrome P450 2C19 in North Indian subjects. Clinical Pharmacology and Therapeutics 63: 422–427. https://doi.org/10.1016/S0009-9236(98)90037-6
- Lamba JK, Lin YS, Schuetz EG (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Advanced Drug Delivery Reviews 54: 1271–1294. https://doi.org/10.1016/S0169-409X(02)00066-2
- Man M, Farmen M, Dumaual C (2010) Genetic variation in metabolizing enzyme and transporter genes: Comprehensive assessment in 3 major east Asian subpopulations with comparison to Caucasians and Africans. Journal of Clinical Pharmacology 50: 929–940. https://doi.org/10.1177/0091270009355161
- Murray CJ, Lopez AD (1996) Evidence-based health policy—lessons from the global burden of disease study. Science 274: 740–743. https://doi.org/10.1126/science.274.5288.740
- Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990–2020: Global burden of disease study. Lancet 349: 1498–1504. https://doi.org/10.1016/S0140-6736(96)07492-2
- Noehr-Jensen L, Zwisler ST, Larsen F (2009) Impact of CYP2C19 phenotypes on escitalopram metabolism and an evaluation of pupillometry as a serotonergic biomarker. European Journal of Clinical Pharmacology 65: 887–894. https://doi.org/10.1007/s00228-009-0657-0
- Ota T, Kamada Y, Hayashida M (2015) Combination analysis in genetic polymorphisms of drug-metabolizing enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in the Japanese population. International Journal of Medical Sciences 12: 78–82. https://doi.org/10.7150/ijms.10263
- Oyehaug E, Ostensen ET, Salvesen B (1984) High-performance liquid chromatographic determination of citalopram and four of its metabolites in plasma and urine samples from psychiatric patients. Journal of Chromatography. A 308: 199–208. https://doi.org/10.1016/0378-4347(84)80209-1
- Pastoor D, Gobburu J (2014) Clinical pharmacology review of escitalopram for the treatment of depression. Expert Opinion on Drug Metabolism & Toxicology 10: 121–128. https://doi.org/10.1517/17425255.2014.863873
- Pastoor D, Gobburu J (2014) Clinical pharmacology review of escitalopram for the treatment of depression. Expert Opinion on Drug Metabolism & Toxicology 10: 121–128. https://doi.org/10.1517/17425255.2014.863873
- Rao N (2007) The clinical pharmacokinetics of escitalopram. Clinical Pharmacokinetics 46: 281–290. https://doi.org/10.2165/00003088-200746040-00002
- Rochat B, Amey M, Van Gelderen H (1995) Determination of the enantiomers of citalopram, its demethylated and propionic acid metabolites in human plasma by chiral HPLC. Chirality 7: 389–395. https://doi.org/10.1002/chir.530070602
- Rudberg I, Hendset M, Uthus LH (2006) Heterozygous mutation in CYP2C19 significantly increases the concentration/dose ratio of racemic citalopram and escitalopram (S-citalopram). Therapeutic Drug Monitoring 28: 102–105. https://doi.org/10.1097/01.ftd.0000189899.23931.76
- Tsai MH, Lin KM, Hsiao MC (2010) Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response. Pharmacogenomics 11: 537–546. https://doi.org/10.2217/pgs.09.168
- Tsuchimine S, Ochi S, Tajiri M, Suzuki Y, Sugawara N, Inoue Y (2018) Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients with Depression. Therapeutic Drug Monitoring 40: 356–361. https://doi.org/10.1097/FTD.0000000000000506
- Waade RB, Hermann M, Moe HL (2014) Impact of age on serum concentrations of venlafaxine and escitalopram in different CYP2D6 and CYP2C19 genotype subgroups. European Journal of Clinical Pharmacology 70: 933–940. https://doi.org/10.1007/s00228-014-1696-8
- Xie HG (2000) Genetic variations of S-mephenytoin 4¢-hydroxylase (CYP2C19) in the Chinese population. Life Sciences 66: 175–181. https://doi.org/10.1016/S0024-3205(00)00446-X
- Xie HG, Prasad HC, Kim RB, Stein CM (2002) CYP2C9 allelic variants: Ethnic distribution and functional significance. Advanced Drug Delivery Reviews 54: 1257–1270. https://doi.org/10.1016/S0169-409X(02)00076-5
- Yasui-Furukori N, Tsuchimine S, Kubo K (2016) The effects of fluvoxamine on the steady-state plasma concentrations of escitalopram and desmethylescitalopram in depressed Japanese patients. Therapeutic Drug Monitoring 38: 483–486. https://doi.org/10.1097/FTD.0000000000000303
- Zhou , Duan W (2009) The role of CYP2C19 polymorphism in the metabolism of escitalopram. Expert Opinion on Drug Metabolism & Toxicology 5(9): 1107–1114.