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All Journal JFIOnline Keluwih: Jurnal Kesehatan dan Kedokteran Jurnal Multidisiplin Madani (MUDIMA) Pharmaceutical Sciences and Research (PSR) Eduvest - Journal of Universal Studies Jurnal Farmasi Indonesia
Yahdiana Harahap
Departemen Farmasi FMIPA, Universitas Indonesia
Aerospace Engineering Agriculture, Biological Sciences & Forestry Civil Engineering, Building, Construction & Architecture Computer Science & IT Decision Sciences, Operations Research & Management Economics, Econometrics & Finance Health Professions Industrial & Manufacturing Engineering Medicine & Pharmacology Neuroscience Nursing Public Health Social Sciences

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Association between CYP2C9 and CYP2C19 Polymorphism, Metabolism, and Neurotoxicity after Administration of Phenytoin: A Systematic Review Mardhiani, Rizka; Harahap, Yahdiana; Wiratman, Winnugroho
Keluwih: Jurnal Kesehatan dan Kedokteran Vol. 5 No. 1 (2023): Keluwih: Jurnal Kesehatan dan Kedokteran (December)
Publisher : Direktorat Penerbitan dan Publikasi Ilmiah, Universitas Surabaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24123/kesdok.V5i1.6010

Abstract

Abstract—Phenytoin is an antiepileptic drug (AED) metabolized by cytochrome P450 enzymes, especially by CYP2C9 (90%) and CYP2C19 (10%), where both enzymes are polymorphic so that they can undergo polymorphism and it can change the metabolic rate of the drug. Phenytoin is one of the drugs whose risk of side effects may increase due to its narrow therapeutic window of 10-20 µg/mL if the metabolism is slow. The main literature was taken from publications through the library databases in 2017 – 2021. Studies and reviews describing the metabolism, CYP2C9 and CYP2C19 polymorphisms, and neurotoxicity of phenytoin were included, and unrelated research were excluded. There were 18 of 853 articles describing CYP2C9 and CYP2C19 polymorphisms, metabolism, and neurotoxicity events associated with phenytoin used. The authors conclude that based on the results from various literature, there is an association between CYP2C9 and CYP2C19 polymorphism, metabolism, and neurotoxicity after Phenytoin administration with CYP2C9*2 and CYP2C9*3 types of polymorphisms for CYP2C9 and CYP2C19*2 and CYP2C19*3 types for CYP2C19*3 enzymes which can slow down the phenytoin metabolism and increase its concentration in serum so that the risk of causing neurotoxicity. Keywords: CYP2C9, CYP2C19,metabolism, neurotoxicity, phenytoin Abstrak—Fenitoin merupakan obat antibangkitan yang dimetabolisme oleh enzim sitokrom P450 terutama oleh CYP2C9 (90%) dan CYP2C19 (10%), dimana kedua enzim tersebut bersifat polimorfik sehingga dapat mengalami polimorfisme dan dapat mempengaruhi laju metabolisme obat. fenitoin merupakan salah satu obat yang risiko efek sampingnya dapat meningkat jika metabolismenya lambat karena jendela terapeutiknya yang sempit, yaitu 10-20 µg/mL. Literatur utama diambil dari publikasi melalui database perpustakaan tahun 2017 – 2021. Penelitian dan ulasan yang menggambarkan metabolisme, polimorfisme CYP2C9 dan CYP2C19, dan neurotoksisitas fenitoin, dan penelitian yang tidak terkait dikeluarkan. Terdapat 18 dari 853 artikel yang menjelaskan polimorfisme CYP2C9 dan CYP2C19, metabolisme, dan kejadian neurotoksisitas terkait dengan fenitoin yang digunakan. Peneliti menyimpulkan bahwa berdasarkan hasil dari berbagai literatur, terdapat hubungan antara polimorfisme, metabolisme, dan neurotoksisitas CYP2C9 dan CYP2C19 setelah pemberian fenitin dengan jenis polimorfisme CYP2C9*2 dan CYP2C9*3 untuk CYP2C9 dan CYP2C19*2 dan CYP2C19*3 jenis enzim CYP2C19*3 yang dapat memperlambat metabolisme fenitoin dan meningkatkan konsentrasinya dalam serum sehingga berisiko menyebabkan neurotoksisitas. Kata kunci: CYP2C9, CYP2C19, fenitoin, metabolisme, neurotoksisitas
Solid Lipid Nanoparticles (SLN): Formulation and Fabrication Punu, Gabriella F.; Harahap, Yahdiana; Anjani, Qonita Kurnia; Hartrianti, Pietradewi; Donnelly, Ryan F.; Ramadon, Delly
Pharmaceutical Sciences and Research Vol. 10, No. 2
Publisher : UI Scholars Hub

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Abstract

Solid lipid nanoparticles (SLN) have emerged as a novel drug delivery system and have been utilized for delivering various kinds of drugs since the 1990s. These particles may consist of multiple solid lipids, including glycerides, waxes, and fatty acids, and can be stabilized by a wide range of surfactants. SLN have garnered significant attention from researchers due to its innovative and versatile nature. Moreover, such delivery system has numerous advantages over traditional colloidal carriers, such as liposomes, polymeric nanoparticles, and emulsions. Several research groups have been developing SLN formulations and fabrication techniques based on their intended purpose, and this research number is still increasing globally. Given the vast potential for the development of SLN in the future, coupled with the wide variety of materials and techniques to be considered during the manufacturing process, this paper provides an extensive overview of the general introduction of SLN, their benefits and drawbacks, and the numerous excipients which can be associated with the SLN formulation. Various aspects related to the models of drug incorporation and fabrication methods are also systematically discussed in this review. In addition, an analysis of the factors that impact the stability of the SLN will also be documented to provide further insight for future advancements in SLN research.
Recent Updates on Dried Blood Spot and Volumetric Absorptive Microsampling as Microsampling Technique for Antiepileptic Drug Determination: A Systematic Review Pridilla, Asmiladita; Harahap, Yahdiana; Purwanto, Denni Joko; Maggadani, Baitha Palanggatan
Pharmaceutical Sciences and Research Vol. 11, No. 2
Publisher : UI Scholars Hub

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Abstract

Implementation of Therapeutic Drug Monitoring (TDM) can be useful for patients with uncontrolled seizures. This review article aims to collect and compare the recent development of bioanalytical methods for antiepileptic drugs using microsampling techniques, namely DBS (Dried Blood Spot) and VAMS (Volumetric Absorptive Microsampling). Studies were searched through databases, namely Science Direct, Pubmed, and the Google Scholar search engine using pre-determined keywords. Studies published between 2019 and 2024 and used micro-sampling techniques for antiepileptic drug analysis were included. Non-English studies, non-related studies, duplication, and full text unavailable were excluded. Primary sources were used to build a conclusion regarding the purpose of this review article. A total of 342 articles were identified from databases. From 8 primary studies included, analytical methods for 21 drug compounds as antiepileptic agents and 4 of their metabolites in DBS and VAMS were found. A summary of sample preparation, analytical method, and validation were presented in the narrative form of this review. Concentrations measured using DBS and VAMS demonstrate a strong correlation with conventional matrices; however, conversion factors based on the blood-to-plasma ratio are necessary for accurate comparison. Additionally, the comparison results between DBS and VAMS technique for TDM is still unsatisfactory to prove their interchangeability. Therefore, this comparison needs further evaluation with more samples and more analytes. Analysis of antiepileptic drugs using VAMS is also still limited and further optimization can be carried out to produce more stable, sensitive, fast, and suitable for TDM practice.
Challenges of Monitoring Blood Levels of Bedaquiline in Drug-Resistant Tuberculosis: A Narrative Review Isra, Nur; Sari, Santi Purna; Harahap, Yahdiana; Handayani, Raden Rara Diah
Eduvest - Journal of Universal Studies Vol. 5 No. 3 (2025): Eduvest - Journal of Universal Studies
Publisher : Green Publisher Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59188/eduvest.v5i3.50267

Abstract

Bedaquiline, a second-line drug for drug-resistant tuberculosis (MDR-TB), is one of the latest generation drugs in the treatment of tuberculosis (TB). However, the challenge in determining the optimal dose and individual pharmacokinetic variability requires the implementation of Therapeutic Drug Monitoring (TDM). This article aims to evaluate the challenges of TDM bedaquiline through a narrative review of the current literature. Relevant articles were identified through computerized searches on PubMed and Google Scholar using a combination of keywords related to bedaquiline, pharmacokinetics, and TDM. Limited clinical data indicate a lack of standard exposure targets and reliable efficacy thresholds. Pharmacokinetic variability is influenced by factors such as age, weight, gender, genetics, comorbidities, and serum albumin. Technical challenges include the need for precise analytical methods and the accessibility of technology in clinical practice. The use of TDM for bedaquiline offers the potential to improve the efficacy of MDR-TB treatment, but more research is needed to address pharmacokinetic variability and develop standardized guidelines.
Microsampling and conventional sampling techniques for quantification of tacrolimus in blood samples: A systematic review Hanifah, Muthia; Harahap, Yahdiana; Purwanto, Denni Joko
Eduvest - Journal of Universal Studies Vol. 4 No. 6 (2024): Journal Eduvest - Journal of Universal Studies
Publisher : Green Publisher Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59188/eduvest.v4i6.1395

Abstract

Tacrolimus is immunosuppressive drugs that have a narrow therapeutic range, and a large inter-patient variability in their pharmacokinetics. Serial monitoring of tacrolimus after transplantation is important to ensure the concentration in biological fluids is maintained at the therapeutic range. Blood sampling for therapeutic drug monitoring of tacrolimus is mostly by venipuncture, making it inconvenient and invasive due to repeated sampling. Thus, microsampling has been adopted as an alternative for sample collection as it is less invasive and more convenient for patients. This article aims to review validated bioanalysis methods for tacrolimus to compare the methods using venous sample and microsampling methods. Related studies about tacrolimus analysis method in blood samples were screened from several databases and summarized with PRISMA flow diagram. A total of 12 studies were considered eligible and reviewed in this article. This systematic review provides a narrative of sample quantification of tacrolimus that collected by venipuncture and microsampling method, its bioanalytical method employed to perform the analysis, and clinical validation or application to patients with organ transplants. Studies with microsampling methods have been validated and applied to the patients. Some studies that compared both methods concluded there is no significant difference between tacrolimus concentrations by venipuncture or microsampling methods. Therefore, microsampling can be considered an option for future development of sampling method in tacrolimus routine monitoring.
The The Effect of Using Different Anticoagulant Types for Determination of Esomeprazole Levels in Human Plasma by High-Performance Liquid Chromatography Mardhiani, Rizka; Harahap, Yahdiana; Sitepu, Eme Stepani; Sunarsih
Jurnal Multidisiplin Madani Vol. 3 No. 10 (2023): October, 2023
Publisher : PT FORMOSA CENDEKIA GLOBAL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55927/mudima.v3i10.4170

Abstract

Esomeprazole is a Proton Pump Inhibitor (PPI) drug formulated in delayed-release tablets, that are included in the mandatory bioequivalence test. In vitro method validation used human plasma from the Indonesian Red Cross that used citrate as an anticoagulant. In the implementation of in vivo study, usually using human plasma used EDTA or heparin as an anticoagulant. This study aims to evaluate the effect of using anticoagulant types that may affect the analysis of esomeprazole in human plasma. Optimum chromatographic conditions used column C18 SunfireTM (5 μm, 250 mm x 4.6 mm); column temperature 40°C; mobile phase acetonitrile - phosphate buffer (40:60% v/v) pH 7.6; 1.0 mL/min flow rate with lansoprazole as an internal standard and wavelength 300 nm (PDA). The extraction was carried out by liquid-liquid extraction method using 500 μl plasma and 5 ml dichloromethane as extraction solvent. The result showed that the concentration range of calibration curve linearity in 5 – 1500 ng/mL. Recovery and broad peak response data of esomeprazole in plasma have significant differences between heparin-EDTA and citrate-EDTA anticoagulants (p<0.05), but there is no significant difference for the stability test. In conclusion, heparin is better than EDTA as an anticoagulant for esomeprazole bioanalysis
Co-Authors . Harmita . Hayun . Hayun Achmad Noerkhaerin Putra Aldrat, Hendri Aldrat, Hendri Andranilla, Rr. Kirana Ani Susanti Ani Susanti Anjani, Qonita Kurnia Baitha Palanggatan Maggadani, Baitha Palanggatan Bambang Karsono Binsar Simanjuntak Binsar Simanjuntak, Binsar Chairunnisa, Dian Fitri Christine Estherina Christine Estherina, Christine Citra Nur Azizah Citra Nur Azizah, Citra Nur Cosphiadi Irawan Dadang Kusmana DENNI JOKO PURWANTO, DENNI JOKO Donnelly, Ryan F. Erilia Kesumahati Erny Sagita, Erny Fadlina Chany Saputri Handayani, Raden Rara Diah Hanifah, Muthia Harmita Harmita Harmita Harmita, Harmita Harryanto Reksodiputro, Harryanto Hartrianti, Pietradewi Hayun Hayun Hayun Hayun, Hayun Heffen, Wan Lelly Heffen, Wan Lelly Herman Suryadi Indah Widyaningsih Isra, Nur Krismartina, Mirna Krismartina, Mirna Letitia Tania, Letitia Loedfiasfiati Alawiyah Maksum Radji Mardhiani, Rizka Maryati Kurniadi Mun'im, Abdul Nadia Farhanah Syafhan Nasution, Azlaini Yus Noorwati Sutandyo Nu Alia Nu Alia, Nu Permata Sari, Kartika Citra Dewi Pridilla, Asmiladita Punu, Gabriella F. Punu, Gabriella Frederika Rahmania, Tesia Aisyah Ramadhani, Dwi Asih RAMADON, DELLY Renesteen, Editha Santi Purna Sari Sherly Meilianti Sherly Meilianti, Sherly Sitepu, Eme Stepani Sri Wardatun Sunarsih Theresia Sinandang Theresia Sinandang, Theresia Trisina, Jessica Umar Mansur Umar Mansur Umar Mansur, Umar Wan Lelly H Wardhani, Bantari Wisynu Kusuma Wiratman, Winnugroho