https://hdl.handle.net/10259/11209 2026-08-18T15:32:16Z https://hdl.handle.net/10259/11925 Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines García-Alfonso, P.; Saiz Rodríguez, Miriam; Mondéjar, R.; Salazar, J.; Páez, D.; Borobia, A. M.; Safont, M. J.; García-García, I.; Colomer, R.; García-González, X.; Herrero, M. J.; López-Fernández, L. A.; Abad-Santos, F. 5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines. 2022-03-01T00:00:00Z https://hdl.handle.net/10259/11924 “Pharmacogenetics of siponimod: A systematic review” by Díaz-Villamarín et al. – Information is power Zubiaur, Pablo; Saiz Rodríguez, Miriam; Abad‐Santos, Francisco On August 12, 2022, Biomedicine and Pharmacotherpy published a systematic review on the pharmacogenetics of siponimod by Díaz-Villamarín et al. [1] We would like to acknowledge the work done by the authors, as siponimod is a drug that may occupy a priority place in the management of secondarily progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity. Therefore, we believe that research aimed at clarifying the impact of genetic variants on the effectiveness and safety of this drug is needed; therefore, we applaud the authors’ efforts with this systematic review. We consider that there are several inconsistencies in the therapeutic recommendations contained in the siponimod drug label and in those issued by the two most relevant international associations in pharmacogenetics: the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). 2023-01-01T00:00:00Z https://hdl.handle.net/10259/11920 Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers Saiz Rodríguez, Miriam; Ochoa, Dolores; Zubiaur, Pablo; Navares-Gómez, Marcos; Román, Manuel; Camargo-Mamani, Paola; Luquero-Bueno, Sergio; Villapalos-García, Gonzalo; Alcaraz, Raquel; Mejía-Abril, Gina; Santos-Mazo, Estefanía; Abad-Santos, Francisco For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study on healthy participants. This is the first investigation to consider demographic characteristics alongside all transporters involved in metformin distribution. Pharmacokinetic parameters of metformin were found to be affected by age, sex, ethnicity, and several polymorphisms. Age and SLC22A4 and SLC47A2 polymorphisms affected the area under the concentration-time curve (AUC). However, after adjusting for dose-to-weight ratio (dW), sex, age, and ethnicity, along with SLC22A3 and SLC22A4, influenced AUC. The maximum concentration was affected by age and SLC22A1, but after adjusting for dW, it was affected by sex, age, ethnicity, ABCG2, and SLC22A4. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by SLC22A3. The volume of distribution and clearance was affected by sex, age, ethnicity and SLC22A3. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in ABCB1, SLC2A2, SLC22A2, or SLC47A1. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization. 2023-03-01T00:00:00Z https://hdl.handle.net/10259/11919 Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives Sanz-Solas, Antonio; Labrador, Jorge; Alcaraz, Raquel; Cuevas, Beatriz; Vinuesa, Raquel; Cuevas, María Victoria; Saiz Rodríguez, Miriam Multiple myeloma (MM) is a hematological neoplasm for which different chemotherapy treatments are used with several drugs in combination. One of the most frequently used drugs for the treatment of MM is the proteasome inhibitor bortezomib. Patients treated with bortezomib are at increased risk for thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, infection, and fatigue. This drug is almost entirely metabolized by cytochrome CYP450 isoenzymes and transported by the efflux pump P-glycoprotein. Genes encoding both enzymes and transporters involved in the bortezomib pharmacokinetic pathway are highly polymorphic. The response to bortezomib and the incidence of adverse drug reactions (ADRs) vary among patients, which could be due to interindividual variations in these possible pharmacogenetic biomarkers. In this review, we compiled all pharmacogenetic information relevant to the treatment of MM with bortezomib. In addition, we discuss possible future perspectives and the analysis of potential pharmacogenetic markers that could influence the incidence of ADR and the toxicity of bortezomib. It would be a milestone in the field of targeted therapy for MM to relate potential biomarkers to the various effects of bortezomib on patients. 2023-04-01T00:00:00Z