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Garcia-Ortiz, José Elias; Fricke, Ingrid; Fariñas, Humberto; Gaviño-Vergara, Alejandro; Camacho-Molina, Alejandra; Gálvez, Marcela; Polo-García, José; Guillén-Navarro, Encarna; Llerena Ruiz, Adrián
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0091pmid: 39814711
Tonk, Megha; Gupta, Vishal; Dhwaj, Amar; Sachdeva, Monika
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0024pmid: 39331538
AbstractIntroduction3-Dimensional printing (3DP) is an additive manufacturing (AM) technique that is expanding quickly because of its low cost and excellent efficiency. The 3D printing industry grew by 19.5 % in 2021 in spite of the COVID-19 epidemic, and by 2026, the worldwide market is expected to be valued up to 37.2 billion US dollars.ContentScience Direct, Scopus, MEDLINE, EMBASE, PubMed, DOAJ, and other academic databases provide evidence of the increased interest in 3DP technology and innovative drug delivery approaches in recent times.SummaryIn this review four main 3DP technologies that are appropriate for pharmaceutical applications: extrusion-based, powder-based, liquid-based, and sheet lamination-based systems are discussed. This study is focused on certain 3DP technologies that may be used to create dosage forms, pharmaceutical goods, and other items with broad regulatory acceptance and technological viability for use in commercial manufacturing. It also discusses pharmaceutical applications of 3DP in drug delivery and drug screening.OutlookThe pharmaceutical sector has seen the prospect of 3D printing in risk assessment, medical personalisation, and the manufacture of complicated dose formulas at a reasonable cost. AM has great promise to revolutionise the manufacturing and use of medicines, especially in the field of personalized medicine. The need to understand more about the potential applications of 3DP in medical and pharmacological contexts has grown over time.
Apellaniz-Ruiz, Maria; Barrachina, Jordi; Castro-Sanchez, Paula; Comes-Raga, Ana; García-González, Xandra; Gil-Rodriguez, Almudena; Lopez-Lopez, Elixabet; Maroñas, Olalla; Morón, Rocío; Muriel, Javier; Olivera, Gladys G.; Riera, Pau; Saiz-Rodríguez, Miriam; Salvador-Martín, Sara; Sans-Pola, Carla; Tejera-Pérez, Hugo; Velasco-Ruiz, Alejandro; Verde, Zoraida; Wang, Daniel; Rodríguez-Vicente, Ana E.; Nunez-Torres, Rocio; ,
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0042pmid: 39523122
AbstractIntroductionPharmacogenetics (PGx) has the potential to improve patient care, allowing to transform medical interventions by providing personalized therapeutic strategies. Scientific evidence supports the use of PGx in clinical practice and international organizations are developing clinical guidelines to facilitate the utilization of PGx testing. However, clinical implementation of PGx is limited and unequal worldwide.ContentThis review summarizes regional and national Spanish initiatives to implement PGx in the clinical practice.Summary and OutlookDiverse strategies to implement PGx in healthcare are applied across countries or even in the different regions of a specific country. Such was the case of Spain, a European country with 17 Autonomous Regions and two Autonomous Cities, each one with capacity to manage their own healthcare systems. Nevertheless, during the past years, many initiatives and strategies have been launched in Spain to develop different aspects of PGx. Importantly, the National Healthcare System has approved a PGx testing catalogue. This review highlights the crucial work and efforts of scientific societies (like the Spanish Society of Pharmacogenetics and Pharmacogenomics), of experts in PGx, of healthcare providers and of governmental parties in the implementation of PGx to personalize patient therapy, focused in Spain.
Torso, Nadine de Godoy; Rodrigues-Soares, Fernanda; Altamirano, Catalina; Ramírez-Roa, Ronald; Sosa-Macías, Martha; Galavíz-Hernández, Carlos; Terán, Enrique; Peñas-LLedó, Eva; Dorado, Pedro; LLerena, Adrián
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0093pmid: 39663234
AbstractThe CYP2C19 enzyme is implicated in the metabolism of several clinically used drugs. Its phenotype is usually predicted by genotyping and indicates the expected enzymatic activity for each patient. However, with a few exceptions, CYP2C19 genotyping has not resulted in a reliable prediction of the metabolizer status, since most of the evidence currently available for this prediction comes from research into populations of predominantly European ancestry. Therefore, this review discusses the main factors that may alter the expected phenotype, as well as the urgent need to include ethnically diverse populations in further studies, so that, in the long term, it is possible to establish guidelines appropriate to these groups.
Bagher, Amina M.; Aboud, Rania A.; Alkinaidri, Noura M.; Aljilani, Saja A.; Hareeri, Rawan H.; Binmahfouz, Lenah S.; Bagher, Sara M.
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0015pmid: 39501421
AbstractObjectivesIbuprofen, a widely used non-steroidal anti-inflammatory (NSAID) for managing pain and inflammation in pediatric patients, is metabolized by the CYP2C8 enzyme. Studies suggest that the CYP2C8*2, *3, and *4 variations of the CYP2C8 gene diminish ibuprofen metabolism, increasing the risk of adverse reactions. The aim of this study was to determine the frequency of the CYP2C8*2, *3, and *4 alleles and genotypes in a pediatric population attending the King Abdulaziz University dental clinic and compare our findings to those of other populations.MethodsA cross-sectional study was conducted with 140 healthy Saudi children ages 6–12. Saliva samples were collected using Oragene™ DNA Sample Collection Kits and analyzed for polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe study identified that CYP2C8*2 AA, AT, and TT genotypes occurred at frequencies of 87.86 %, 9.29 %, and 2.86 %, respectively. For CYP2C8*3, AA, AG, and GG genotypes were found in 87.14 , 8.75, and 4.29 % of subjects, respectively. The CYP2C8*4 allele was less frequent, with CC and CG genotypes at 97.86 % and 2.14 %, respectively, and the GG genotype was absent. Allele frequencies for CYP2C8*2, *3, and *4 were 7.5 %, 8.57 %, and 1.07 %, respectively.ConclusionsOur findings reveal that the allelic frequencies for the CYP2C8 polymorphisms in the Saudi pediatric cohort are substantially elevated compared to those reported in other Asian populations. This suggests Saudis may experience more varied drug responses, especially for medications that undergo metabolism by the CYP2C8 enzyme, like ibuprofen.
Aloui, Ghaith; Charfi, Rym; Daldoul, Mouna; Ben Hammamia, Syrine; Ben Sassi, Mouna; Zouari, Mohamed; Eljeberi, Hanene; Daghfous, Riadh; Gaies, Emna; Trabesli, Sameh
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0043pmid: 39679494
AbstractObjectivesWhile the existing literature extensively covers the topic of tacrolimus variability, it remains crucial to gather data that are tailored to the Tunisian population. Our primary goal was to assess the variability in tacrolimus bioavailability using the Cp(0)/weight dosage ratio in Tunisian kidney transplant patients. We also aimed to determine the correlations between blood trough level (Cp(0)) and the area under the concentration–time curve (AUC0–12 h) in this cohort.MethodsThis retrospective study included patients treated with oral tacrolimus for the prevention of organ rejection between 2009 and 2023. The correlation between parameters was analyzed through a Pearson coefficient and a regression model. We assessed the inter- and intraindividual variability by calculating the coefficient of variation for patients with at least three samples.ResultsAnalysis of 2,124 samples revealed a weak correlation (R=0.121) between Cp(0) and weight dosage. We found that 79.3 % of patients exhibited high variability in the Cp(0)/weight dosage ratio. A strong correlation (R=0.797) was found between Cp(0) and the AUC0–12 h. We also found that 47.6 % of patients showed high variability in the AUC0–12 h/Cp(0) ratio.ConclusionsThis study underscores the necessity for individualized therapeutic drug monitoring in Tunisian kidney transplant recipients due to the high variability in the Cp(0)/weight dosage ratio. The AUC0–12 h/Cp(0) ratio is proposed as a more consistent parameter for therapeutic drug monitoring, offering potential improvements in tacrolimus therapy management.
Qureshi, Almas; Rahman, Rais ur; Shamsi, Yasmeen
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0070pmid: 39523832
AbstractObjectivesUrinary tract infection (UTI) is one of the most frequent reasons for prescribing antibiotics. Escherichia coli implicated in 75–90 % cases of UTI is becoming increasingly resistant to antibiotics. Finding alternative therapeutic agent for this infection is critical, for which herbal drugs may be an option. In Unani medicine, urinary tract infection (Ṭa’diya Majra-i-Bawl) is treated with herbal drugs possessing Da’fe Ufoonat (antiseptic), Muhallilat (anti-inflammatory) and Mudirrat (diuretic) properties. Polyherbal formulations of such drugs are expected to be beneficial in treating Escherichia coli infection. The aim of the study was to assess the efficacy and safety of a Unani polyherbal formulation aimed to develop a safe and efficacious drug for the treatment of urinary tract infection (Ṭa’diya Majra-i-Bawl) caused by Escherichia coli.MethodsThis open-label, single armed clinical study was conducted on patients with clinical signs and symptoms of UTI and positive urine culture for E. coli. Patients were treated with the polyherbal formulation consisting of 50 % hydro-alcoholic extracts of Khar Khasak (Tribulus terrestris), Bhui Amla (Phyllanthus niruri), Kabab Cheeni (Piper cubeba), Beekh -i-Kasni (Cichorium intybus), Beekh-i-Karafs (Apium graveolens), Asl-us-Soos (Glycyrrhiza glabra), and Giloy (Tinospora cordifolia) in a dose of one capsule (500 mg) thrice a day orally with plain water for 42 days.ResultsMaximum (83 %) urine cultures turned out negative for E. coli after the completion of therapy.ConclusionsPolyherbal Unani formulation was found to be very effective for the treatment of Urinary tract infection. Clinical and microbiological cure was achieved in maximum number of patients and drug was very well tolerated without any adverse/side effect.
Sabbagh, Bassel Al.; Palanirajan, Vijayaraj Kumar; Chew, Yik-Ling; Chin, Jin Han; Ahmad, Mariam; Akowuah, Gabriel Akyirem
2024 Drug Metabolism and Personalized Therapy
doi: 10.1515/dmpt-2024-0005pmid: 39658558
AbstractObjectivesVernonia amygdalina Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of V. amygdalina is consumed as a vegetable due to its medicinal and nutritional properties. The present study focused on the quantification of bioactive compounds, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, and 1,5-O-dicaffeoylquinic acid from aqueous leaf extract of V. amygdalina. The study also aims to investigate the effects of the aqueous leaf extract of V. amygdalina on cytochrome P450 2C9 (CYP2C9), and cytochrome P450 3A4 (CYP3A4) in hepatic cells of control and diabetic rats.MethodsThe quantification of the bioactive compounds was conducted using ultra-high-performance liquid chromatography multiple reactions monitoring tandem mass spectrometry (UHPLC-MS/MS-MRM) technique. The effect of the extract on CYP2C9 and CYP3A4 activities was determined using a fluorometric screening kit according to the manufacturer’s instructions.ResultsThe three bioactive compounds were detected and quantified in the aqueous leaf extract. Results showed that the content of luteolin-7-O-glucuronide (47 μg/mg) was the highest followed by luteolin-7-O-glucoside (3.5 μg/mg) and 1,5-O-dicaffeoylquinic acid (1.07 μg/mg). The extract showed an inhibitory effect on CYP3A4 and CYP2C9 enzyme activities in control and diabetic rats.ConclusionsThe UHPLC-MS/MS-MRM method is sensitive and reliable for the quality control of V. amygdalina leaf extract. The inhibitory effect of the extract suggests that concomitant use of V. amygdalina leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction.
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