Drug metabolism and personalized therapy最新文献

Objectives: Rhinitis is classified into several types with allergic rhinitis (AR) being the most common. AR is among the inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), in which corticosteroids are administered to overcome the decrease in cortisol production. The treatment options available for AR vary with 1^st line treatment being intranasal corticosteroids (INCS). The responsiveness to corticosteroids is due to their binding to corticotropin-releasing hormone receptor-1 (CRHR1). Various studies have studied the responsiveness to corticosteroids treatment in patients with asthma and COPD in association with CRHR1 gene single nucleotide polymorphisms (SNPs).

Methods: In our study, we investigated the association of three SNPs of CRHR1 gene (rs242941, rs242940, and rs72834580) with symptoms improvement post-treatment in AR patients. Blood samples were collected from 103 patients for DNA extraction and gene sequencing. Those patients started to receive INCS for 8 weeks and their symptoms were assessed, through a questionnaire, before treatment and post-treatment to check for symptoms improvement.

Results: Our data showed that improvement of eye redness is significantly less following INCS treatment in patients with allele (C) (AOR=0.289, p-value-0.028, 95 % CI=0.096-0.873) and genotype (CC) (AOR=0.048, p-value-0.037, 95 % CI=0.003-0.832) of rs242941 SNP. There was no correlation with other genotypes, alleles, or haplotypes of the investigated SNPs.

Conclusions: Our findings show that there is no correlation between CRHR1 gene polymorphism and symptoms improvement following INCS treatment. Further studies are required to evaluate the association of INCS and symptoms improvement post-treatment with larger sample size.

Objectives: Development of the secondary to ACEI cough leads to discontinuation of the drugs of this group. Assessing the safety of the ACEIs with further development of customized approaches for their administration is a major scientific and practical problem. The objective of this study was to assess the association of the genetic markers with the development of the adverse drug reaction in the form of secondary to enalapril dry cough in the patients with essential arterial hypertension.

Methods: Study involved 113 patients with the secondary to enalapril cough and 104 patients without development of the secondary to enalapril adverse drug reaction.

Results: The patients carriers of the genotype AA rs2306283 of gene SLCO1B1 had 2-fold higher odds of developing the dry cough than those with the genotypes AG and GG (ОR=2.01, 95%CI=1.10-3.66, р=0.023). Similarly, the patients heterozygous for rs8176746 of gene АВО had 2.3-fold higher odds of developing the ADR in the form of dry cough than the carriers of the genotypes GG and TT (ОR=2.30, 95%CI=1.24-4.29, р=0.008).

Conclusions: Statistically significant association between the development of the ADR in the form of secondary to enalapril dry cough and polymorphisms rs2306283 of gene SLCO1B1 and rs8176746 of gene ABO was revealed.

Objectives: This real-world study was conducted to assess the adverse effects following immunization (AEFI) and immunogenicity of ChAdO×1 nCoV-19 vaccine in terms of neutralising antibody titers and to study the effects of covariates such as age, sex, comorbidities and prior COVID status on these outcomes. Also, the effectiveness of the vaccine based on interval between the two doses was also investigated.

Methods: A total of 512 participants (M/F=274/238) aged 35(18-87) years comprising a mixed population of healthcare workers, other frontline workers and general public were enrolled between March and May 2021. Records for adverse events if any were collected telephonically by following up with participants up to 6 months post first dose and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5. Blood samples for measuring antibody titers against the receptor binding domain (RBD) were collected serially using a convenient sampling strategy up to 6 months after the first dose. Data on breakthrough COVID infection was collected telephonically till December 2021.

Results: Incidence of local reactions was higher after first dose at 33.4 % (171/512) compared to those after second dose at 12.9 % (66/512). Commonest side effect observed was injection site pain after the first (87.1 %; 149/171) and second (87.9 %; 56/66) dose respectively. Among systemic reactions, fever was the most common manifestation followed by myalgia and headache. Female sex (p<0⸱001) and age less than 60 years (p<0⸱001) had significantly higher predilection for systemic toxicities. Age ≤60 years (p=0.024) and prior-COVID (p<0.001) were found to be significantly associated with higher antibody titers, however, no association was found between these variables and breakthrough COVID infection. Longer spacing between the doses (≥6 weeks) was found to offer better protection against breakthrough infection compared to a spacing of 4 weeks. All breakthroughs were mild-moderate in severity, not requiring hospitalization.

Conclusions: The ChAdOx1 nCov-19 vaccine is apparently safe and effective against SARS-CoV-2 virus infection. Prior COVID infection and younger age group achieve higher antibody titers, but no additional protection. Delaying the second dose up to at least 6 weeks is more effective compared to shorter spacing between doses.

Objectives: A study was conducted to develop and validate the warfarin pharmacogenetic dose optimization algorithm considering the clinical pharmacogenetic implementation consortium (CPIC) recommendations for the Asian ethnicity population.

Methods: The present prospective observational study recruited warfarin-receiving patients. We collected a three ml blood sample for VKORC1, CYP2C9*2, CYP2C9*3, and CYP4F2 polymorphism assessment during the follow-up visits. Clinical history, sociodemographic and warfarin dose details were noted.

Results: The study recruited 300 patients (250 in derivation and 50 in validation timed cohort) receiving warfarin therapy. The baseline characteristics were similar in both cohorts. BMI, presence of comorbidity, VKORC1, CYP2C9*2, and CYP2C9*3 were identified as covariates significantly affecting the warfarin weekly maintenance dose (p<0.001 for all) and the same were included in warfarin pharmacogenetic dose optimization algorithm building. The algorithm built-in the present study showed a good correlation with Gage (r=0.57, p<0.0001), and IWPC (r=0.51, p<0.0001) algorithms, widely accepted in western side of the globe. The receiver operating characteristic curve analysis showed a sensitivity of 73 %, a positive predictive value of 96 %, and a specificity of 89 %. The algorithm correctly identified the validation cohort's warfarin-sensitive, intermediate reacting, and resistant patient populations.

Conclusions: Validation and comparisons of the warfarin pharmacogenetic dose optimization algorithm have made it ready for the clinical trial assessment.

Objectives: Unani physicians have suggested a wide range of anti-dermatophytic remedies, although the scientific evidence is scarce. Thus, the efficacy and safety of Terminalia chebula Retz. fruit powder mixed with vinegar was compared with terbinafine hydrochloride 1% cream in the treatment of tinea corporis in order to establish the non-inferiority of test drugs.

Methods: The primary outcome measures were change in the presence or absence of hyphae on KOH mount test, change in pruritus severity assessed on 100 mm VAS and change in physician's global assessment. Secondary outcome measure was change in the dermatology life quality index (DLQI). Hemograms, serum creatinine, serum bilirubin, and random blood sugar levels were measured at the baseline and after treatment to ensure the safety of the interventions.

Results: A per-protocol analysis was done on 40 participants (21 in the test group and 19 in the control group). The observed differences in the primary and secondary outcomes between the test and control groups were greater than the non-inferiority margin, signifying that the test drugs were not inferior.

Conclusions: It may be inferred that the trial drug Terminalia chebula Retz. fruit powder mixed with vinegar is not inferior to terbinafine hydrochloride cream in the treatment of tinea corporis.

Objectives: Cassia singueana is widely used in northern Nigeria as an herb for the treatment of enamors ailments. Nevertheless the toxicity of the herb on liver architecture; the hepatic lobule and body weight is yet to be authenticated.

Methods: A total of 24 male Wistar rats with an average weight of 150 g were randomly placed into four groups. Each group consisted of 6 rats. Group A served as the control group while groups B, C and D were given 150, 300, and 450 mg of Cassia singueana leaves extract respectively for 14 days. The animals were weighed before, during and after the treatment phase subsequently, they were sacrificed and the liver tissues were processed and stained using hematoxylin and eosin (H&E) stain, Masson's and Trichrome Stain, Gordon and Sweet's Stain, and Periodic Acid Schiff (PAS)Stain.

Results: There was no significant change in the animal's body weight of in all the groups when compared to the control group. Our histology result showed that Cassia singueana induced vascular lesion and hepatocytes degeneration putatively though mechanism of cell death (apoptosis and necrosis). It was also found that Cassia singueana has no toxic effect on the reticular fibers of the liver. High dose of Cassia singueana was found to induce the deposition of PAS positive materials in hepatocytes.

Conclusions: The Cassia singueana leaves extract induce hepatocyte degeneration and vascular lesion in the hepatic lobules of the wistar rats, without affecting the animals' body weight.

Objectives: Abha Guggulu (AG) is a traditional Ayurvedic herbal formulation used for treating joint disorders and bone fractures. Individually, the ingredients are known for their promising anti-inflammatory and rejuvenating actions. The present study attempts to explore the anti-arthritic potential of AG through an exploratory clinical trial.

Methods: The study was conducted using a quasi-experimental model. The clinical trial has been registered in Clinical Trials Registry of India (registration number: CTRI/2019/09/021354). Osteoarthritis patients of both genders (n=12, 40-70 years age group), meeting the inclusion/exclusion criteria, were recruited in the single arm study. AG was administered in tablet form in a dose of 1.5 g, twice daily. The WOMAC score was used as a primary outcome measure. The WOMAC scale of patients was recorded on 0th, 15th and 30th days of treatment.

Results: At the end of treatment, there was a significant difference in the scores of the outcome measure. As per WOMAC total score, participants were significantly improved (p=0.002) after consuming the drug for 1 month.

Conclusions: Overall, the data indicates significant improvement of subjects in both scales and objective measures used for assessment purposes. There were no adverse drug reactions reported during the trial. AG may be used as a safe and effective supplement to reduce symptoms of osteoarthritis. The clinical efficacy of the formulation might be mediated through the synergistic blend of herbal bioactive compounds from AG.

Objectives: Evaluating the knowledge in pharmacogenomics (PGx) is the first step toward the implementation of PGx testing in clinical practice. This survey aimed to evaluate the knowledge of PGx testing among healthcare providing students at the top-ranked university in the West Bank of Palestine.

Methods: First an online questionnaire consisting of 30 questions regarding the demographic, knowledge, and attitude toward pharmacogenomics testing was structured and validated. Then the questionnaire was distributed to 1,000 current students from different fields.

Results: 696 responses was received. The results showed that almost half of the participants (n=355, 51.1%) have never took any courses about PGx during their university training. Only 81 (11.7%) of the students who took the PGx course stated that it helped them understanding how genetic variations affect drug response. The majority of the students were uncertain (n=352, 50.6%) or disagreed (n=143, 20.6%) that the lectures during university education described the effects of genetic variants on drug response. Although most of the students (70-80%) answered that genetic variants can indeed affect the drug's response, only 162 students (23.3%) responded that VKORC1 and CYP2C9 genotypes influence the response to warfarin. In addition, only 94 (13.5%) students were aware that many medicine labels include clinical information about PGx testing provided by the FDA.

Conclusions: It is concluded from the results of this survey that there is a lack of exposure to PGx education associated with poor knowledge of PGx testing among the healthcare providing students in the West Bank of Palestine. It is recommended to include and improve the lectures and courses regarding PGx as this will have a major impact on precision medicine.