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Abstrak :
Latar Belakang: Pengobatan antimalaria dan anti-HIV secara bersamaan merupakan tantangan baru dalam penanganan koinfeksi malaria dan HIV. Primakuin merupakan substrat sekaligus inhibitor bagi CYP3A4, sedangkan ritonavir merupakan substrat, inhibitor, sekaligus inducer bagi CYP3A4. Tujuan penelitian ini adalah untuk mengukur ekspresi mRNA CYP3A4 pada kultur sel HepG2 yang diinduksi oleh pemberian primakuin dan ritonavir secara bersamaan. Metode: Pada penelitian pendahuluan, sel HepG2 diinkubasi dengan primakuin 30, 40, 50 uM; ritonavir 2, 10, 20 uM; DMSO <0,1 % sebagai kontrol negatif; atau rifampisin 20 uM sebagai kontrol positif. Adapun pada penelitian dengan perlakuan kombinasi obat, sel HepG2 diinkubasi dengan primakuin 40 uM+ritonavir 10 uM; DMSO <0,1 %; atau rifampisin 20 uM selama 72 jam. Sel dipanen menggunakan tripsin-EDTA dan RNA total diekstraksi menggunakan reagensia isolasi tripure. Setelah jumlah RNA total dikuantifikasi menggunakan alat spektrofotometer, ekspresi mRNA CYP3A4 diukur dengan real-time reverse transcription polymerase chain reaction (RT-PCR). Hasil: Terjadi peningkatan ekspresi mRNA CYP3A4 (1,22 kali lipat terhadap kontrol) pada sel HepG2 yang diinkubasi dengan primakuin dan ritonavir secara bersamaan. Hal ini menunjukkan bahwa efek induksi oleh ritonavir lebih dominan daripada efek inhibisi oleh primakuin. Kesimpulan: Pemberian primakuin dan ritonavir secara bersamaan meningkatkan ekspresi mRNA CYP3A4 in vitro.

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Abstract
Background: Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment. Methods: For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin?EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine. Conclusion: Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. (Med J Indones 2012;21:3-7) Keywords: CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir

Abstrak :
Pelayanan kefarmasian di apotek saat ini berorientasi pada kebutuhan pasien berdasarkan kondisi klinis atau penyakit. Pada beberapa kasus, pasien yang menebus resep pada apotek memiliki jumlah obat melebihi satu atau resep polifarmasi sehingga apoteker berperan dalam pengkajian dan analisis terkait efek samping dan interaksi dari obat-obat setiap bulan. Pengkajian dilakukan pada dua resep polifarmasi bulan Februari 2023 di Apotek Roxy Depok secara klinis melalui literatur klinis kemudian dilanjutkan dengan analisis mekanisme masing-masing obat dan mekanisme interaksi terhadap obat-obat lainnya terhadap kondisi klinis pasien sehingga diperoleh rekomendasi peresepan polifarmasi. Berdasarkan proses tersebut, resep polifarmasi 1 diperoleh 4 jenis efek samping yang tidak diresepkan obat lain dan 6 jenis interaksi obat yang perlu diedukasi serta resep polifarmasi 2 diperoleh 3 jenis efek samping yang tidak diresepkan obat lain, 1 jenis efek samping yang diresepkan obat lain, dan 1 jenis interaksi obat yang perlu diedukasi. ...... Pharmaceutical services in pharmacies are currently oriented towards the needs of patients based on clinical conditions or diseases. In some cases, patients who fill prescriptions at the pharmacy have more than one drug or polypharmacy prescriptions, so pharmacists play a role in assessing and analyzing the side effects and interactions of drugs every month. The review was conducted on two polypharmacy prescriptions in February 2023 in Roxy Pharmacy Depok clinically through clinical literature then continued with the analysis of the mechanism of each drug and the mechanism of interaction with other drugs against the patient's clinical condition to obtain recommendations for polypharmacy prescribing. Based on this process, polypharmacy prescription 1 obtained 4 types of side effects that were not prescribed other drugs and 6 types of drug interactions that needed to be educated and polypharmacy prescription 2 obtained 3 types of side effects that were not prescribed other drugs, 1 type of side effect that was prescribed other drugs, and 1 type of drug interaction that needed to be educated.

Abstrak :
Pendahuluan: PGK merupakan penyakit yang sering memiliki beberapa komorbid sehingga perlu menggunakan berbagai terapi kombinasi obat. Oleh sebab itu, polifarmasi sering dilakukan dan salah satu konsekuensinya adalah terjadinya potensi interaksi obat (PIO). PIO dianggap sebagai masalah pengobatan yang dapat dicegah, namun dalam praktik klinis dapat mengakibatkan efek samping obat (ESO) atau reaksi obat yang merugikan. Hal tersebut tentu akan mempengaruhi klinis dan keberhasilan pengobatan serta keamanan penggunaan obat pada pasien PGK. Penelitian ini bertujuan untuk mengetahui pola peresepan pasien PGK dan pengaruhnya terhadap potensi interaksi dan efek samping obat yang dicurigai akibat interaksi obat. Metode: Penelitian ini merupakan penelitian non eksperimental dan pengambilan data dilakukan secara potong lintang pada pasien PGK rawat jalan stadium 3-5 pre-dialisis di rumah sakit Cipto Mangunkusumo (RSCM) dalam periode Januari 2019 sampai dengan Desember 2020. Data diambil dari electronic health record dan pusat rekam medis RSCM. Rujukan potensi interaksi obat menggunakan software Micromedex. Hasil: Terdapat 106 pasien yang memenuhi persyaratan dan diambil menjadi subjek penelitian. Hasil penelitian menunjukkan bahwa pada pasien PGK rawat jalan stadium 3- 5 pre-dialisis di RSCM tahun 2019-2020, terdapat 111 jenis obat yang diresepkan dan obat yang paling sering diresepkan adalah bisoprolol (36,5%). Proporsi pasien yang mendapatkan pengobatan dengan potensi interaksi obat adalah 76% (81 pasien), sedangkan proporsi pasien yang mengalami ESO yang dicurigai akibat interaksi obat adalah 28% (23 pasien) dari 81 pasien dengan PIO. ESO tersebut berupa hiperglikemi (17 pasien), hipertensi (1 pasien), hiperkalemi (1 pasien) dan hipotensi (1 pasien). Terdapat hubungan yang bermakna secara statistik antara variabel perancu yaitu, jumlah obat > 10, komorbid jantung dan DM dengan ESO yang dicurigai akibat interaksi obat (p<0.05). Hasil multivariat mendapatkan hanya komorbid jantung (gagal jantung dan penyakit jantung koroner) yang memiliki hubungan yang bermakna secara statistik dengan ESO yang dicurigai akibat interaksi obat (p = 0,03). Kesimpulan: Pada penelitian ini, sebanyak 76% pasien mendapatkan pengobatan dengan PIO. Sedangkan 28% pasien dari 81 pasien dengan PIO mengalami ESO yang dicurigai akibat interaksi obat. ESO yang paling banyak dialami adalah hiperglikemi. Komorbid jantung merupakan faktor risiko terjadinya ESO yang dicurigai akibat interaksi obat. ......Introduction: CKD often has several comorbidities so it is necessary to use various drug combination therapies. Therefore, it can lead to polypharmacy and one of its consequences is the occurrence of potential drug-drug interactions (DDI). DDI is considered a problem that can be prevented, but in clinical practice it can result in adverse drug reactions (ADR). This will certainly affect the clinical and treatment success as well as the safety of the drug use in CKD patients. This study was aimed to determine the prescribing pattern and its effect on potential DDI and ADR that are suspected due to DDI. Methods: This was a non-experimental cross-sectional study, conducted on CKD outpatients stage 3-5 pre-dialysis at Cipto Mangunkusumo Hospital in the period January 2019 to December 2020. Data were taken from electronic health records and the hospital’s medical record. The Micromedex software was used as a reference for potential drug interactions. Results: There were 106 patients who met the requirements and were taken as research subjects. The results showed that in CKD out-patients stage 3-5 pre-dialysis at RSCM in 2019-2020, there were 111 types of drugs prescribed and the most frequently prescribed drug was bisoprolol (36.5%). The proportion of patients who received treatment with a potential DDI was 76% (81 patients), while the proportion of patients who experienced ADR suspected due to DDI was 28% (23 patients) from 81 patients with suspected DDI. The ADRs were hyperglycemia (17 patients), hypertension (1 patient), hyperkalemia (1 patient) and hypotension (1 patient). There was a statistically significant association between the confounding variables, namely, number of drugs, cardiovascular disease and DM with ADR suspected due to DDI (p<0.05). Multivariate analysis found that only cardiovascular disease (congestive heart failure and coronary artery disease) had a statistically significant relationship with ADR suspected due to DDI (p = 0.03). Conclusion: In this study, 76% of patients received treatment with potential DDI. Meanwhile, 23% from 81 patients patients with DDI experienced ADR suspected due to drug interactions. The most often occuring ADR is hyperglycemia. It was found that cardivascular comorbidity is a risk factor for having an ADR suspected cause by DDI.

Abstrak :
Drug-drug interactions in pharmaceutical development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage.

Abstrak :
Latar belakang: Penelitian ini dilakukan untuk meneliti pengaruh pemberian ritonavir dan primakuin bersamaan, yang diberikan dalam dosis tunggal atau dosis berulang pada konsentrasi plasma ritonavir pada tikus. Metode: Pada studi dengan pemberian dosis tunggal, 30 tikus Sprague Dawley jantan secara acak diberikan ritonavir 20 mg/kgBB atau ritonavir 20 mg/kgBB + primakuin 1,2 mg/kgBB atau ritonavir 20 mg/kgBB + ketokonazol 10 mg/kgBB. Ketokonazol digunakan sebagai kontrol positif penghambat metabolisme ritonavir. Pada studi dengan pemberian dosis berulang, 30 tikus Spraque Dawley secara acak diberikan ritonavir 20 mg/kgBB/hari atau ritonavir 20 mg/kgBB/hari + primaquine 1,2 mg/kgBB/hari atau ritonavir 20 mg/kgBB/hari + rifampisin 100 mg/kgBB/day. Rifampisin digunakan sebagai kontrol positif penginduksi metabolisme ritonavir. Hasil: Pada pemberian dosis tunggal, ketokonazol meningkatkan area dibawah kurva kadar plasma (AUC) ritonavir (↑114,8%, p< 0.05), sedangkan primakuin cenderung menurunkan AUC ritonavir (↓32,6%, p> 0.05). Pemberian dosis berulang menunjukkan bahwa rifampisin menurunkan AUC ritonavir (↓42,8%, p< 0.001), dan primakuin menurunkan AUC ritonavir (↓ 46,6%, p< 0.001). Kesimpulan: Pemberian primakuin dan ritonavir bersamaan dapat menurunkan AUC ritonavir. Hal ini dapat menyebabkan konsentrasi ritonavir sebagai anti-HIV tidak mencukupi, sehingga dapat menyebabkan kegagalan terapi dengan ritonavir.

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Abstract
Background: The present study was aimed to explore the effects of ritonavir and primaquine combination given as a singledose or repeated-dose compared to ritonavir alone on ritonavir plasma concentration in the rats. Methods: In single-dose study, 30 male Spraque Dawley rats were randomly allocated to receive ritonavir 20 mg/kg BW or ritonavir 20 mg/kg BW + primaquine 1.2 mg/kg BW or ritonavir 20 mg/kg BW + ketokonazole 10 mg/kg BW. Ketokonazole was used as positive control of ritonavir metabolism inhibitor. In the repeated-dose study, thirty Spraque Dawley male rats were randomly allocated to receive ritonavir 20 mg/kg BW/day or ritonavir 20 mg/kg BW/day + primaquine 1.2 mg/kg BW/day or ritonavir 20 mg/kg BW/day + rifampicin 100 mg/kg BW/day. Rifampicin was used as a positive control of ritonavir metabolism inducer. Results: In the single-dose study, ketokonazole increased the area under the plasma concentration (AUC) of ritonavir (↑114.8%, p< 0.05), while primaquine tended to decrease the AUC of ritonavir (↓ 32.6%, p> 0.05). Repeated-dose study showed that rifampicin decreases the AUC of ritonavir (↓ 42.8%, p< 0.001), and primaquine decreased the AUC of ritonavir plasma concentration (↓ 46.6%, p< 0.001). Conclusion: Concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect may result in the insuffi cient concentration of ritonavir as anti-HIV, which may lead to treatment failure with ritonavir.

Abstrak :
Tujuan Penyesuaian dosis dan pemilihan jenis obat penting dilakukan dalam keadaan gangguan fungsi ginjal. Penelitian observasional ini bertujuan untuk mengetahui ketepatan penyesuaian dosis dan ketepatan pemilihan obat pada pasien di ruang rawat inap Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Indonesia/Rumah Sakit Dr. Cipto Mangunkusumo, Jakarta. Metode Pasien usia 18 tahun atau lebih dengan bersihan kreatinin <60 mL/menit berdasarkan rumus Cockroft-Gault diikutkan dalam penelitian ini. Obat yang dinilai adalah obat yang ekskresinya terutama melalui ginjal dan obat-obat yang bersifat nefrotoksik. Ketepatan pemilihan dinilai berdasarkan ada/tidaknya kontraindikasi dan interaksi potensial antar obat yang digunakan, sedangkan ketepatan penyesuaian dosis didasarkan pada berbagai literature buku teks dan brosur obat. Data dikumpulkan antara bulan May sampai July 2007. Hasil Dari 43 pasien yang memenuhi kriteria inklusi, didapatkan pemakaian obat sebanyak 385 jenis, 164 jenis di antaranya mempunyai jalur ekskresi utama di ginjal dan/atau bersifat nefrotoksik. Dari 164 jenis obat tersebut, penyesuaian dosis dilakukan dengan tepat pada 142 jenis obat (86.5%), sedangkan penyesuaian yang tidak tepat terdapat pada 22 jenis obat (13.5%). Terdapat 1 pemakaian obat yang merupakan kontraindikasi, dan 15.1% dinilai potensial berinteraksi. Kesimpulan Penyesuaian dosis dan pemilihan obat pada pasien gangguan fungsi ginjal di ruang rawat inap Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Indonesia/Rumah Sakit Dr. Cipto Mangunkusumo telah dilakukan dengan baik.

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Aim Dose adjusment and drug selection is important in patient with renal dysfuction.This study was aimed to assess the accuracy of dose adjustment and drug selection for renal dysfunction patient at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital, Jakarta. Methods Patients ≥ 18 years old with estimated creatinine clearance < 60 mL/minute based on Cockroft-Gault formula were included in this study. The drugs assessed were those excreted by the kidney or having nephrotoxic effect. The appropriateness of drug selection is assessed based on the preserce or not contraindication or potential of drug-drug interaction. The accuracy of dose adjustment were assessed based on information available in various textbooks, literatures, and drug brochures. Data were collected between May to July 2007. Results Data obtained from 43 patients met the inclusion criterias demonstrated that 164 out of 385 drug prescriptions were mainly eliminated by the kidney or have nephrotoxic characteristic. Out of 164 drug prescriptions, 142 (86.5%) were appropriately adjusted, while the other 22 (13.5%) were inappropriately adjusted for the dose. There was only one contraindication for the usage of the drug and 15.1% potentially drug interaction. Conclusion Dose adjustment and drug selections in patients with renal dysfunction at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital are conducted appropriately.

Abstrak :
The aim of this research is to reveal the relationship between the physician?s qualification and the rationality of the prescribing oral cardiovascular drugs to adult patients from drugs interactions point of view. This research is classified into descriptive analitic retrospectif survey. Data was collected from a dispensary located in East Jakarta. The result showed that rate of the rationality of prescribing cardiovascular agents by the physician?s is 89,86%. From total prescribing, 56,45% among them was prescribed by specialist whereas the rest 43,55% was prescribed by general practitioners. The rate of the irrational prescribing is 10,14%. From total prescribing, 78,57% among them was prescribed by general practitioners whereas the rest 21,43% was prescribed by specialist. Based on Chi square test?s result, there is a relationship between physician?s qualification and the rationality of the prescribing oral cardiovascular drug. Specialist physicians more rational compare to general practitioners in prescribing oral cardiovascular drug.