Search Results (23)

Background/Objectives: Direct oral anticoagulants (DOACs) have transformed the prevention of thromboembolic events, but their efficacy and safety remain highly variable across individuals. DD217, a novel oral direct factor Xa inhibitor, has demonstrated potent anticoagulant activity in preclinical and clinical studies. No pharmacogenetic data are currently available for this compound. Based on in silico predictions of metabolic pathways and transporter involvement, and evidence from other DOACs, we hypothesized that variants in CYP2C and P-glycoprotein genes may contribute to variability in pharmacokinetics (PK) and clinical outcomes. Methods: Fifty-two patients undergoing total knee arthroplasty were enrolled, of whom 34 received the investigational drug (40 mg/day, n = 16; 60 mg/day, n = 18). DNA was extracted from peripheral blood cells, and genotyping of CYP2C9, CYP2C19, CYP2C8, CYP3A4, CYP3A5, and ABCB1 was performed by real-time PCR. Pharmacokinetics (PK) parameters (T_max, AUC_last, C_max) were assessed. In silico docking and pathway modeling predicted CYP2C and P-glycoprotein (ABCB1) involvement in drug disposition. Associations of genetic variants with PK parameters and adverse events (thrombosis, bleeding) were analyzed. Results: Carriers of reduced-function CYP2C9 alleles (intermediate [IM] or poor metabolizers [PM]) in the 60 mg group had a significantly shorter T_max compared with normal metabolizers (p = 0.005227), with trends toward higher AUC_last (p = 0.06926) and C_max (p = 0.1259). No significant associations were observed for CYP2C19, CYP3A4/5, or CYP2C8. In contrast, ABCB1 polymorphisms were associated with systemic exposure: carriers of the C allele at rs1045642 had higher AUC_last and C_max compared to TT (wild-type) homozygotes, while rs2032582 T allele carriers showed lower exposure (p < 0.05). At the haplotype level, the C–G–C–T combination of ABCB1 was more frequent in patients with thrombotic events at the 40 mg dose (p = 0.038). Overall, 5 thrombosis events and 1 bleedings were recorded on DD217, with no consistent associations to single SNPs. Conclusions: This first pharmacogenetic evaluation of DD217 shows that CYP2C9 variants are associated with differences in early-phase pharmacokinetics (T_max), while ABCB1 polymorphisms appear to modulate systemic exposure (AUC_last, C_max) and may influence thrombotic risk. These observations are consistent with in silico predictions of metabolic and transporter pathways. Despite limitations in sample size and event frequency, the study highlights the feasibility and importance of early pharmacogenetic evaluation during the drug development cycle of novel DOACs. Full article

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with a fivefold increase in stroke risk. Direct oral anticoagulants (DOACs), including apixaban, are now the preferred therapy for stroke prevention in patients with non-valvular AF (NVAF). However, interindividual variability in drug response and safety remains a major challenge, particularly in elderly patients with comorbidities and polypharmacy. Genetic polymorphisms in drug-metabolizing enzymes and transporters may contribute to variability in apixaban exposure and bleeding risk. This study aimed to evaluate the association of polymorphisms in ABCB1, CYP3A4, and CYP3A5 with steady-state plasma concentrations of apixaban (Cssmin) and hemorrhagic complications in elderly patients with NVAF. Methods: This cross-sectional study included 197 patients (mean age 83 ± 8 years; 67% women) with NVAF treated with apixaban (5 mg twice daily). Genotyping of ABCB1 (rs1045642, rs2032582, rs1128503), CYP3A4*22 (rs35599367), and CYP3A5*3 (rs776746) was performed using allele-specific real-time PCR. Cssmin of apixaban was determined by high-performance liquid chromatography coupled with tandem mass spectrometry. Associations with bleeding events were evaluated. Results: Bleeding events were recorded in 40 patients (20.3%). An association signal was observed for ABCB1 rs1045642, where carriers of the CC genotype had a higher risk of bleeding compared with alternative alleles (OR = 2.805; 95% CI: 1.326–5.935; p = 0.006). After correction for multiple testing, the association remained significant only under the log-additive model (OR = 1.93 per C allele; 95% CI: 1.17–3.20; q = 0.0275; p_adj = 0.044), while recessive and codominant effects did not withstand Bonferroni adjustment. No significant associations were observed for rs2032582, rs1128503, CYP3A4*22, or CYP3A5*3. None of the studied polymorphisms, including rs1045642, significantly affected Cssmin. Concomitant therapy, particularly with antiarrhythmic drugs and statins (rosuvastatin), also increased bleeding risk. Conclusions: The findings highlight the potential contribution of ABCB1 rs1045642 and specific drug–drug interactions to the risk of hemorrhagic complications in elderly NVAF patients receiving apixaban. Full article

Psychotropic medication is commonly used for the treatment of mental health conditions. However, the genetic factors that influence psychotropic medication responses in children have not been thoroughly investigated. To address this gap, a systematic review and thematic analysis were conducted to examine the genetic impact of psychotropic medication response in children. The Down and Blacks and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists assessed the quality of studies and health economics, respectively. Using PRISMA reporting guidelines, 50 articles were identified with a sample size ranging from 2 to 2.9 million individuals. Most of the studies reported on ethnicity, and approximately half of the studies (24/50) were performed in North America. Five themes emerged from the thematic analysis: (1) implications of non-CYP450 polymorphisms, (2) paediatric CYP450 pharmacogenetics, (3) genetic predictors of response, (4) insights for implementation and future research and (5) phenoconversion. The thematic analysis revealed that assessment of non-CYP450 polymorphisms and psychotropic medication response, especially in those with mental health conditions such as autism, would be helpful. Epilepsy onset, risk and treatment response were associated with non-CYP450 genetic variants. Phenoconversion of substrates associated with CYP2D6 and CYP2C19 metabolisers is common in individuals with mental health conditions, and ABCB1 variants can influence psychotropic medication responses. A multidisciplinary model could also help guide clinical decision-making in cases involving complex neurodevelopmental profiles. Using the Down and Blacks checklist, the average score from the 50 studies was 17.7 points (min. 14, max. 24). The health economic evaluation of studies using the CHEERS checklist gave an average score of 33.0% (range: 21.4% to 35.7%). The study provides an important resource of information for healthcare professionals, researchers and policymakers working at the intersection of child psychiatry, pharmacogenomics and precision medicine. Full article

A variable number tandem repeat polymorphism has been described in the CYP2C9 promoter (pVNTR) with three types of fragments: short (pVNTR-S), medium (pVNTR-M), and long (pVNTR-L). The pVNTR-S allele appears in strong linkage disequilibrium (LD) with the non-functional CYP2C9*3 allele in populations of European ancestry, but independently of this, it also appears to reduce the level of CYP2C9 expression in human liver by up to 34%. Objectives: This study, in a Dominican population with varying amounts of Western European, African, and Native American ancestry, aims primarily to determine the frequency of CYP2C9 pVNTR, and the degree of LD of pVNTR-S with CYP2C9*3. Secondarily, it explores if the frequency of the pVNTR-S allele is over- or under-represented in those with a greater component of African ancestry. Methods: A total of 193 healthy volunteers from the Dominican Republic participated in the study. The promoter region of CYP2C9 was amplified and analyzed by capillary electrophoresis. Analyses of CYP2C9 genotypes (*2, *3, *5, *6, and *8) and genetic ancestry, estimated in 176 Dominican individuals by genotyping 90 ancestry informative markers, were previously performed in this population. Results: The frequencies of CYP2C9 pVNTR-L, M, and S variants are 0.065, 0.896, and 0.039, respectively. LD between pVNTR-S and CYP2C9*3 was found (D’ = 0.756, r² = 0.702) to be weaker than in European populations. Conclusions: Populations with a greater African ancestry component appear to present a lower-than-expected frequency of pVNTR-S, as well as a lower tendency for this and CYP2C9*3 alleles to be inherited together, as is common in Europeans. The present exploratory results warrant further research in vivo about the effects of pVNTR-S in predicting CYP2C9 activity. Its inclusion in CYP2C9 testing panels for personalized drug therapy could be relevant in populations such as the Dominican, where the LD between pVNTR-S and CYP2C9*3 is low. Full article

Aim: To assess the impact of the CYP2C82 polymorphism on chloroquine and desethylchloroquine concentrations in patients with malaria caused by P. vivax. Methods: A prospective study was conducted on patients with malaria in an endemic area of the Amazon basin. Liquid chromatography was employed to measure the levels of chloroquine and desethylchloroquine, while molecular methods estimated the frequency of the CYP2C82 variant. Results: This study revealed that plasma levels of chloroquine were higher in patients with the CYP2C82 polymorphism compared to those without this variant. The difference in plasma levels ranged from 5% to 26.5%. Conversely, patients with the CYP2C82 polymorphism exhibited lower levels of desethylchloroquine. Conclusion: The findings of this study confirm the impairment of chloroquine metabolism by the CYP2C82 variant. However, it is noteworthy that in the dose regimen used for malaria treatment, these changes did not lead to toxic concentrations of the drug. Full article

Difenoconazole (DIF), a demethylation inhibitor fungicide, was registered in 2016 for the control of postharvest diseases of pome fruits. In this study, 162 isolates from P. expansum (n = 31) and 13 other “non-expansum” Penicillium spp., i.e., P. solitum (n = 52), P. roqueforti (n = 32), P. commune (n = 15), P. paneum (n = 9), P. psychrosexuale (n = 8), P. crustosum (n = 5), P. carneum (n = 3), P. palitans (n = 2), along with one isolate each of P. citrinum, P. griseofulvum, P. raistrickii, P. ribium, and P. viridicatum, were collected from multiple packinghouses in the U.S. Pacific Northwest. In vitro sensitivity assays showed similar sensitivities of spores and mycelia across species with the mean EC₅₀ values ranging from 0.01 for P. psychrosexuale (n = 8) to 1.33 μg mL⁻¹ for P. palitans (n = 2), whereas the mean EC_50s were 0.03, 0.12, 0.19, and 0.51 μg mL⁻¹ for P. expansum (n = 31), P. paneum (n = 9), P. solitum (n = 52), and P. crustosum (n = 5), respectively. The recommended rate of DIF controlled P. expansum and P. roqueforti isolates but not all isolates of four other Penicillium spp. on Fuji apples after five months at 1.5 °C. The mixture of DIF + fludioxonil (FDL) (Academy^TM) controlled all the dual-sensitive isolates (DIF^SFDL^S) and DIF single-resistant (DIF^R) isolates among the six species tested but not the FDL^R and dual DIF^RFDL^R isolates. Notable polymorphism was detected in the CYP51 gene of the “non-expansum” species with four mutations located at four residues. Although the isolates analyzed in this study had not previously been exposed to DIF, the findings indicate variable sensitivity levels among the Penicillium spp. Full article

Our preliminary research proposed the cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and hydroxyacyl-coenzyme A dehydrogenase trifunctional multienzyme complex beta subunit (HADHB) genes as candidates for association with milk-production traits in dairy cattle because of their differential expression across different lactation stages in the liver tissues of Chinese Holstein cows and their potential roles in lipid metabolism. Hence, we identified single-nucleotide polymorphisms (SNPs) of the CYP7A1 and HADHB genes and validated their genetic effects on milk-production traits in a Chinese Holstein population with the goal of providing valuable genetic markers for genomic selection (GS) in dairy cattle, This study identified five SNPs, 14:g.24676921A>G, 14:g.24676224G>A, 14:g.24675708G>T, 14:g.24665961C>T, and 14:g.24664026A>G, in the CYP7A1 gene and three SNPs, 11:g.73256269T>C, 11:g.73256227A>C, and 11:g.73242290C>T, in HADHB. The single-SNP association analysis revealed significant associations (p value ≤ 0.0461) between the eight SNPs of CYP7A1 and HADHB genes and 305-day milk, fat and protein yields. Additionally, using Haploview 4.2, we found that the five SNPs of CYP7A1 formed two haplotype blocks and that the two SNPs of HADHB formed one haplotype block; notably, all three haplotype blocks were also significantly associated with milk, fat and protein yields (p value ≤ 0.0315). Further prediction of transcription factor binding sites (TFBSs) based on Jaspar software (version 2023) showed that the 14:g.24676921A>G, 14:g.24675708G>T, 11:g.73256269T>C, and 11:g.73256227A>C SNPs could alter the 5′ terminal TFBS of the CYP7A1 and HADHB genes. The 14:g.24665961C>T SNP caused changes in the structural stability of the mRNA for the CYP7A1 gene. These alterations have the potential to influence gene expression and, consequently, the phenotype associated with milk-production traits. In summary, we have confirmed the genetic effects of CYP7A1 and HADHB genes on milk-production traits in dairy cattle and identified potential functional mutations that we suggest could be used for GS of dairy cattle and in-depth mechanistic studies of animals. Full article

Fluoxetine is one of the most prescribed antidepressants, yet it still faces challenges due to high intersubject variability in patient response. Mainly metabolized by the highly polymorphic gene CYP2D6, important differences in plasma concentrations after the same doses are found among individuals. This study investigated the association of fluoxetine pharmacokinetics (PK) with pharmacogenetic variants. A bioequivalence crossover trial (two sequences, two periods) was conducted with fluoxetine 20 mg capsules, in 24 healthy subjects. Blood samples for fluoxetine determination were collected up to 72 h post-dose. Subjects were genotyped and single nucleotide variants (SNV) were selected using a candidate gene approach, and then associated with the PK parameters. Bioequivalence was confirmed for the test formulation. We found 34 SNV on 10 genes with a quantifiable impact on the PK of fluoxetine in the randomized controlled trial. Out of those, 29 SNVs belong to 7 CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5), and 5 SNVs to 3 genes impacting the pharmacodynamics and efficacy of fluoxetine (SLC6A4, TPH1, ABCB1). Moreover, decreased/no function SNVs of CYP2D6 (rs1065852, rs28371703, rs1135840) and CYP2C19 (rs12769205) were confirmed phenotypically. Our research contributes to deepening the catalog of genotype-phenotype associations in pharmacokinetics, aiming to increase pharmacogenomics knowledge for rational treatment schemes of antidepressants. Full article

Background: Pharmacogenomic factors affect the susceptibility to drug–drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of 290 older adults and analysed the prevalence of gene polymorphisms that can increase their interacting potential. We also pinpointed clinical decision support systems (CDSSs) that incorporate pharmacogenomic factors in DDI risk evaluation. Methods: Perpetrator drugs were identified using the Drug Interactions Flockhart Table, the DRUGBANK website, and the Mayo Clinic Pharmacogenomics Association Table. Allelic variants affecting their activity were identified with the PharmVar, PharmGKB, dbSNP, ensembl and 1000 genome databases. Results: Amiodarone, amlodipine, atorvastatin, digoxin, esomperazole, omeprazole, pantoprazole, simvastatin and rosuvastatin were perpetrator drugs prescribed to >5% of our patients. Few allelic variants affecting their perpetrator activity showed a prevalence >2% in the European population: CYP3A4/5*22, *1G, *3, CYP2C9*2 and *3, CYP2C19*17 and *2, CYP2D6*4, *41, *5, *10 and *9 and SLC1B1*15 and *5. Few commercial CDSS include pharmacogenomic factors in DDI-risk evaluation and none of them was designed for use in older adults. Conclusions: We provided a list of the allelic variants influencing the activity of drug perpetrators in older adults which should be included in pharmacogenomics-oriented CDSSs to be used in geriatric medicine. Full article

Purpose: To evaluate the association of CYP1A2 and ADORA2A gene polymorphisms, paraxanthine concentrations, and habitual caffeine (CAF) intake with respect to muscular performance after acute CAF supplementation. Methods: A total of 27 resistance-trained males participating in the study ingested either 5 mg/kg of CAF or PL 45 min before a battery of exercise tests in a cross-over design. DNA was tested for the rs5751876 and rs762551 polymorphisms. Results: CAF improved performance in jumping average power, average velocity, max velocity, bench press in the first set, and peak power in the second set. For the CYP1A2 genotype, C allele carriers improved in jumping average velocity (CAF: 1.77 ± 0.14 m/s, PL: 1.71 ± 0.16 m/s, p < 0.001), and AA homozygotes improved set 1 bench press (CAF: 9.7 ± 1.7 reps, PL: 8.9 ± 1.8 reps, p = 0.046). For the ADORA2A genotype, CC (CAF: 1.70 ± 0.20 m/s, PL: 1.67 ± 0.19 m/s, p = 0.005) and CT (CAF: 1.79 ± 0.09 m/s, PL: 1.74 ± 0.11 m/s, p < 0.001) improved in jumping average velocity and CT also improved in bench press set 2 peak power (CAF: 363 ± 76 W, PL: 323 ± 59 W, p = 0.021). For CAF habituation, CAF improved jumping average power (p = 0.007) and jumping average velocity (p < 0.001) in high users but not in low users (p > 0.05). Conclusions: CAF may improve jumping and bench press performance, irrespective of genotypes, but the associations with the genotypes in CYP1A2 and ADORA2A genes, as well as habitual CAF intake, are not clear and require further investigation. Full article

Polymorphisms in CYP2C9 can significantly interfere with the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen. The present research aimed to study the PK/PD parameters of naproxen and its metabolite, 6-O-desmethylnaproxen, associated with allelic variations of CYP2C9. In our study, a rapid, selective, and sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method was developed and validated for the determination of naproxen and its main metabolite, 6-O-desmethylnaproxen, in oral fluid. Naproxen and its main metabolite were separated using a Shim-Pack XR-ODS 75L × 2.0 column and C18 pre-column at 40 °C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v), with an injection flow of 0.3 mL/min. The total analytical run time was 3 min. The volunteers, previously genotyped for CYP2C9 (16 ancestral—CYP2C9 *1 and 12 with the presence of polymorphism—CYP2C9 *2 or *3), had their oral fluids collected sequentially before and after taking a naproxen tablet (500 mg) at the following times: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72 and 96 h. Significant differences in the PK parameters (* p < 0.05) of naproxen in the oral fluid were: Vd/F (L): 98.86 (55.58–322.07) and 380.22 (261.84–1097.99); Kel (1/h): 0.84 (0.69–1.34) and 1.86 (1.09–4.06), in ancestral and mutated CYP2C9 *2 and/or *3, respectively. For 6-O-desmethylnaproxen, no PK parameters were significantly different between groups. The analysis of prostaglandin E2 (PGE₂) proved to be effective and sensitive for PD parameters analysis and showed higher levels in the mutated group (p < 0.05). Both naproxen and its main metabolite, 6-O-desmethylnaproxen, and PGE₂ in oral fluid can be effectively quantified using LC-MS/MS after a 500 mg oral dose of naproxen. Our method proved to be effective and sensitive to determine the lower limit of quantification of naproxen and its metabolite, 6-O-desmethylnaproxen, in oral fluid (2.4 ng/mL). All validation data, such as accuracy, precision, and repeatability intra- and inter-assay, were less than 15%. Allelic variations of CYP2C9 may be considered relevant in the PK of naproxen and its main metabolite, 6-O-desmethylnaproxen. Full article

This study investigated the ability of the Brazilian Caffeine Expectancy Questionnaire (CaffEQ-BR), full and brief versions, to differentiate genetic profiles regarding the polymorphisms of the CYP1A2 (rs 762551) and ADORA2A (rs 5751876) genes in a cohort of Brazilian athletes. One-hundred and fifty participants were genotyped for CYP1A2 and ADORA2A. After the recruitment and selection phase, 71 (90% male and 10% female, regular caffeine consumers) completed the CaffEQ-BR questionnaires and a self-report online questionnaire concerning sociodemographic data, general health status, and frequency of caffeine consumption. The order of completion of the CaffEQ-BR questionnaires was counterbalanced. The concordance between the full and brief versions of the CaffEQ-BR was analyzed using the intraclass correlation coefficient (ICC). To determine the discriminatory capacity of the questionnaires for genotype, the receiver operating characteristic (ROC) curve was applied for sensitivity and specificity (significance level of 5%). Mean caffeine intake was 244 ± 161 mg·day⁻¹. The frequency of AA genotypes for CYP1A2 was 47.9% (n = 34) and 52.1% (n = 37) for C-allele carriers (AC and CC). The frequencies of TT genotypes for ADORA2A were 22.7% (n = 15) and 77.3% (n = 51) for C-allele carriers (TC and CC). All CaffEQ-BR factors, for the full and brief versions, were ICCs > 0.75, except for factor 6 (anxiety/negative effects; ICC = 0.60), and presented ROC curve values from 0.464 to 0.624 and 0.443 to 0.575 for CYP1A2 and ADORA2A. Overall, the CaffEQ-BR (full and brief versions) did not show discriminatory capacity for CYP1A2 and ADORA2A gene polymorphisms. In conclusion, the CaffEQ-BR was not able to differentiate genotypes for the CYP1A2 or ADORA2A genes in this group of Brazilian athletes. Full article

CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice. Full article

Background: This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment. Methods: A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021. Results: Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication–gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/CYP2C9; (2) celecoxib/CYP2C9; (3) piroxicam/CYP2C8, CYP2C9; (4) diclofenac/CYP2C9, UGT2B7, CYP2C8, ABCC2; (5) meloxicam/CYP2C9; (6) aspirin/CYP2C9, SLCO1B1, and CHST2; (7) amitriptyline/CYP2D6 and CYP2C19; (8) imipramine/CYP2C19; (9) nortriptyline/CYP2C19, CYP2D6, ABCB1; and (10) escitalopram/HTR2C, CYP2C19, and CYP1A2. Conclusions: Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the CYP2C9 poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management. Full article

A polymorphism in the gene encoding the metabolic enzyme cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is a particularly influential factor in the use of tacrolimus in Japanese patients. Those who are homozygotic for the *3 mutation lack CYP3A5 activity, which results in substantial individual differences in tacrolimus metabolism. The aim of this study was to analyze the relationship between individual differences in tacrolimus blood concentration changes and CYP3A5 polymorphisms in allogeneic hematopoietic stem cell transplantation recipients during the period of increasing blood concentration of the drug following treatment onset. This was a prospective observational cohort study, involving 20 patients administered tacrolimus by continuous infusion. The subjects were divided into the *1/*3 and *3/*3 groups based on CYP3A5 polymorphism analysis. The tacrolimus blood concentration/dose (C/D) ratio increased from day 1 and was largely stable on day 5, and a significant difference was observed between the *1/*3 and *3/*3 groups in the time course of the C/D ratio during this period (p < 0.05). This study reveals the effects of CYP3A5 polymorphism on continuous changes in tacrolimus blood concentration. Full article