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KR-20260062137-A - Method of prediction the blood concentration of finasteride

KR20260062137AKR 20260062137 AKR20260062137 AKR 20260062137AKR-20260062137-A

Abstract

The present invention relates to a method for predicting the blood drug concentration of finasteride, specifically comprising: (a) a step of detecting an ALT concentration in the blood of an individual; (b) a step of detecting a single nucleotide polymorphism of the CYP3A5 (cytochrome P450) gene in a biological sample of an individual; and (c) wherein the ALT concentration in step (a) is 40 IU/L or higher, and the of step (b) The present invention relates to a method for predicting the drug concentration of finasteride in an individual, comprising the step of determining that the individual has a high drug concentration upon administration of finasteride when the CYP3A5 genotype is CYP3A5*3/*3 or when all of the above conditions are met. Furthermore, the present invention relates to a method for preventing adverse effects of the finasteride drug in an individual by predicting the drug concentration of finasteride in the individual.

Inventors

  • 정승현

Assignees

  • 국립순천대학교산학협력단

Dates

Publication Date
20260507
Application Date
20241025

Claims (6)

  1. (a) a step of detecting ALT concentration in the blood of an individual; (b) a step of detecting single nucleotide polymorphisms of the CYP3A5 (cytochrome P450) gene in a biological sample of an individual; and (c) if the ALT concentration in step (a) is 40 IU/L or higher, the of step (b). A method for predicting the blood drug concentration of a finasteride drug in an individual, comprising the step of determining that the drug concentration of the individual will be high upon administration of the finasteride drug when the single nucleotide polymorphism of the CYP3A5 gene is CYP3A5*3/*3, or when both of the above conditions apply.
  2. A method for predicting the blood drug concentration of finasteride in an individual, wherein step (b) comprises: b-1) a step of collecting a biological sample from an individual and extracting nucleic acid; (b-2) a step of obtaining a polymerase chain reaction product by performing a polymerase chain reaction (PCR) using the nucleic acid extracted in step (b-1) as a template and a primer capable of amplifying the sequence of the CYP3A5 (cytochrome P450) gene or a fragment thereof; and (b-3) a step of detecting single nucleotide polymorphisms of the CYP3A5 gene by analyzing the nucleotide sequence of the polymerase chain reaction product obtained in step (b-2).
  3. A method for predicting the blood drug concentration of an individual for finasteride, characterized in that, in paragraph 2, the primers are the forward primer of SEQ ID NO. 1 and the reverse primer of SEQ ID NO. 2.
  4. A method for predicting the blood drug concentration of a finasteride drug in an individual according to claim 1, wherein the high drug concentration in step (c) is at least 1.1 times the drug concentration of the individual for administration of the finasteride drug when ALT is less than 40 IU/L or the individual's CYP3A5 gene single nucleotide polymorphism is *1/*1 or *1/*3.
  5. A method for preventing adverse effects of the finasteride drug in an individual by administering finasteride to the individual in a reduced dose of 30 to 40% by weight compared to 100% by weight when the individual's ALT is 40 IU/L or higher or the individual's CYP3A5 gene single nucleotide polymorphism is *3/*3, based on the prediction of the individual's blood drug concentration for the finasteride drug of claims 1 to 4.
  6. A method for preventing adverse effects of the finasteride drug in an individual by administering finasteride to the individual in a reduced dose of 40 to 50% by weight compared to 100% by weight when the individual's ALT is less than 40 IU/L or the individual's CYP3A5 gene single nucleotide polymorphism is *3/*3, based on the prediction of the individual's blood drug concentration for the finasteride drug of claims 1 to 4.

Description

Method of predicting the blood concentration of finasteride The present invention relates to a method for predicting the blood drug concentration of finasteride, specifically comprising: (a) a step of detecting an ALT concentration in the blood of an individual; (b) a step of detecting a single nucleotide polymorphism of the CYP3A5 (cytochrome P450) gene in a biological sample of an individual; and (c) if the ALT concentration in step (a) is 40 IU/L or higher, the step (b). The present invention relates to a method for predicting the blood drug concentration of finasteride in an individual, comprising the step of determining that the individual's drug concentration will be high when the CYP3A5 genotype is CYP3A5*3/*3, or when all of the above conditions are met. Furthermore, the present invention relates to a method for preventing adverse effects of the finasteride drug in an individual by predicting the blood drug concentration of finasteride in the individual. Finasteride is a drug belonging to the azasteroid family, which is structurally similar to the male hormone testosterone. Finasteride blocks the conversion of testosterone into dihydrotestosterone (DHT) by pharmacologically inhibiting 5α-reductase. Because DHT has a more potent pharmacological effect than testosterone, finasteride exerts a therapeutic effect by inhibiting physiological activities caused by DHT, such as benign prostatic hyperplasia and masculinization. Clinically, finasteride is primarily used to treat benign prostatic hyperplasia (BPH) and androgenetic alopecia, and it is rarely prescribed to women or children. Generally, a daily dose of 5 mg is recommended for BPH treatment, and 1 mg for androgenetic alopecia. Additionally, for BPH, the dosage may be gradually increased after follow-up observation based on the severity of symptoms. According to recent studies, BPH is the most common disease in men. The incidence of BPH continues to rise due to increased exposure to risk factors such as metabolic diseases and obesity, as well as increased life expectancy. Finasteride requires long-term administration of at least 3 to 6 months to demonstrate efficacy in the treatment of androgenetic alopecia and BPH, as it must maintain 5α-reductase inhibition (Loughlin, 2021). Therefore, efficacy and safety regarding the pharmacokinetic (PK) variability of finasteride are important clinical considerations. Major side effects reported include decreased libido, erectile dysfunction, decreased semen volume, breast enlargement, and rash (Diviccaro et al., 2019). By identifying the key factors affecting the inter-individual variability (IIV) of finasteride pharmacokinetics (PK) and their quantitative correlations, effective clinical trials will be possible to minimize side effects and maximize drug efficacy for each individual. There have been no reported studies on finasteride PK variability within a population, particularly regarding quantitative relationships. In other words, there is a lack of pharmacological information regarding the quantitative PK characteristics and inter-individual PK variability of finasteride, and accessible data is very limited. This acts as a factor causing uncertainty in the establishment of finasteride clinical regimens. Therefore, PK modeling and studies on inter-individual PK variability can serve as the foundation for precision medicine and will significantly contribute to further enhancing safety and efficacy in clinical applications by bridging the pharmacological information gap regarding finasteride. Since finasteride metabolism occurs primarily in the liver (Steiner, 1996), relevant information is only available in the drug leaflet, and it is stated that it should be administered with caution to patients with hepatic impairment. However, despite finasteride being used in clinical practice, dosage and regimens are determined empirically, and scientific data regarding individual management of side effects or prediction of drug efficacy are not accessible. Accordingly, the inventors have made diligent efforts to provide a method for preventing side effects of finasteride and determining the dosage by predicting the in-subject drug concentration for finasteride, for which the dosage and administration are determined empirically and there is no scientific information regarding the management of individual side effects or the prediction of drug efficacy; as a result, the present invention has been completed. Figure 1 is a schematic diagram of an experimental step-by-step workflow according to one embodiment of the present invention. Figure 2 shows the serum concentration profiles of finasteride in 26 Korean men after a single oral administration (10 mg). (A) is the mean serum concentration profile, and (B) is the serum concentration profile by CYP3A5 genotype. The vertical bars represent the standard deviation (SD). Figure 3 is a graph comparing pharmacokinetic parameters of finasteride according to CYP3A5 genotypes ( *1