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Primaquine decreased plasma concentration of ritonavir: single- and repeated-dose study in Sprague Dawley rats

Medical Journal of Indonesia Vol 20, No 3 (2011): August
Publisher : Faculty of Medicine Universitas Indonesia

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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 insufficient concentration of ritonavir as anti-HIV, which may lead to treatment failure with ritonavir. (Med J Indones 2011; 20:190-4)Keywords: drug interaction, metabolism, primaquine, ritonavir

Survei Pengetahuan Dokter Spesialis terhadap Penggunaan Opiat pada Tatalaksana Nyeri Kanker di Rumah Sakit Pemerintah, Jakarta, 2017

Indonesian Journal of Cancer Vol 11, No 4 (2017): October- December 2017
Publisher : Indonesian Journal of Cancer

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Abstract

Treatment of cancer pain often requires opioids, and morphine is a gold standard in the management of severe cancer pain. Inadequate knowledge of cancer pain management causes opioid usage is not optimal. Indonesia is one of the countries with very low opioid consumption. The purpose of this study was to find out the physician’s knowledge about the management of cancer pain in choosing opioid, administration, doses, side effects, addiction and factors of opioid that barrier in pain management. This cross-sectional study was conducted in General Hospital Jakarta and a Private Hospital in Tangerang. Inclusion criteria were medical specialist who treating cancer pain. This study used questionnaires that filled out by respondents and confidential. Score of adequate knowledge was ≥ 70, and to assess the relationship between knowledge of opioid use with specialization analyzed by Chi-square test and Fisher’s exact if Chi-square requirement is not fulfilled. Statistical analysis was performed by SPSS version 20. From a total of 146 distributed questionnaires, we received 103 questionnaires (70,5%). In this study, the majority of respondents (69,9%) had inadequate knowledge. The highest rate (70,55) was found in the choosing opioid section, while the lowest rate (49,5) was found in the opioid side effects section. There is no significant relationship between physician knowledge on opioid usage and specialization (P= 0,355). Government regulation is major obstacle to opioid use, followed by lack of training, drug availability and knowledge of side effects ABSTRAK Penatalaksanaan nyeri kanker sering kali membutuhkan opiat dengan morfin sebagai gold standard menurut panduan WHO analgesic step ladder . Pengetahuan penalaksanaan nyeri kanker yang kurang menyebabkan penggunaan opiat yang tidak optimal. Indonesia merupakan salah satu negara dengan konsumsi opiat yang sangat rendah. Tujuan studi ini adalah untuk mengetahui pengetahuan dokter mengenai penanganan nyeri kanker dalam pemilihan opiat, cara pemberian, dosis, efek samping, dan adanya adiksi, serta faktor-faktor yang menjadi penghambat pada penanganan nyeri kanker. Desain penelitian ini merupakan survei potong lintang ( cross sectional ) yang dilakukan terhadap dokter spesialis yang menangani nyeri kanker di Rumah Sakit Umum Pemerintah Jakarta dan salah satu rumah sakit swasta di Tangerang. Penelitian ini menggunakan kuesioner yang diisi responden dan bersifat rahasia. Pengetahuan dianggap baik bila nilai ≥ 70. Sedangkan untuk menilai hubungan antara pengetahuan tentang penggunaan opiat dengan bidang spesialisasi dokter dianalisis dengan uji Chi-square . Hasil statistik dianalisis dengan menggunakan SPSS versi 20. Dari total 146 kuesioner yang didistribusikan, didapatkan 103 kuesioner (70,5%) yang direspons. Pada penelitian ini, mayoritas responden (69,9%) mempunyai pengetahuan yang tidak adekuat. Rerata tertinggi didapatkan pada bagian pemilihan opiat 70,55; sedangkan rerata terendah didapatkan pada bagian efek samping opiat, yaitu 47,56. Tidak terdapat hubungan bermakna antara pengetahuan dokter tentang penggunaan opiat dengan bidang spesialisasi (P= KORESPONDENSI: Lenny Indrayani Departemen Farmakologi dan Terapeutik, Universitas Indonesia. Email: lenny3ma@gmail.com Indonesian Journal of Cancer Vol. 11, No. 4 October - December 2017160 0,355). Regulasi pemerintah merupakan penghambat utama pada penggunaan opiat, disusul dengan kurangnya pelatihan, ketersediaan obat dan pengetahuan tentang efek samping.

A survey on the appropriateness of drug therapy in patients with renal dysfunction at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital

Medical Journal of Indonesia Vol 18, No 2 (2009): April-June
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

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. (Med J Indones 2009; 18: 108-13)Key words: renal dysfunction, drug interaction, contraindication, dose adjusment

The effects of quercetin on oxidative stress and fibrosis markers in chronic kidney disease rat model

Medical Journal of Indonesia Vol 26, No 3 (2017): September
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Background: Oxidative stress may play a role in the pathogenesis of (CKD), Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cell defense mechanism against oxidative stress. In this study, we examined the effect of quercetin, a polyphenplic antioxidant anti fibrosis compund in fruits and vegetables, on the 5/6 nephrectomy-induced CKD progression model rats through modulation of Nrf2 expression.Methods: Male Sprague-Dawley rats were randomly divided into normal control group (C), untreated 5/6 nephrectomy (Nx), quercetin-treated 5/6 nephrectomy (100 mg/kgBW/day orally) (NxQ), and captopril-treated 5/6 nephrectomy (10 mg/kgBW/day orally) (NxK) for 8 weeks. At the end of study, all animals were sacrified. Urine, blood, and kidney tissues were taken for examination of proteinuria, plasma creatinine, urea, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, Nrf2, Keap1, heme oxygenase-1 (HO-1) expressions, and renal fibrosis.Results: Quercetin administration did not affect the level of protein in urine, plasma creatinine, and urea. However, it tended to reduce the level of MDA, increase GPx activity, Nrf2, Keap1, and HO-1 expression as well as the degree of fibrosis.Conclusion: In 5/6 nephrectomized rats, quercetin tended to ameliorate the level of MDA, GPx activity, Nrf2, Keap1, and HO-1 expression. In addition, quercetin tended to decrease the degree of fibrosis in the remnant kidney.

Cardioprotective Effect of Quercetin in 5/6-Nephrectomized Rats: Focus on Myocardial fibrosis and Oxidative Stress

Jurnal Jamu Indonesia Vol 2 No 3 (2017): Jurnal Jamu Indonesia
Publisher : Pusat Studi Biofarmaka Tropika LPPM IPB; Tropical Biopharmaca Research Center - Bogor Agricultural University

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Abstract

Uremic cardiomyopathy is the leading cause of death in patients with chronic kidney disease. Fluid overload and oxidative stress play important roles in its pathogenesis. This study aims to determine the effect of quercetin on uremic cardiomyopathy in 5/6-nephrectomized rats. To our knowledge, its cardioprotective effect on uremic cardiomyopathy induced in rats by 5/6 nephrectomy has not been investigated yet. Uremia was induced surgically in male Sprague-Dawley rats via 5/6 nephrectomy. Quercetin was administered per orally at a dose of 100 mg/kg/day for 8 weeks prior to sacrifice. Meanwhile, captopril was administered at a dose of 10 mg/kg/day. Lipid peroxidation was assessed using TBARS reaction, while GPX activity was determined to explore the endogen antioxidant mechanism. Myocardial fibrosis was analyzed using Massons’ Trichrome staining and the level of NT-proBNP in plasma was measured as a marker of cardiac dysfunction. Nephrectomy 5/6 had no effects on plasma NT– proBNP levels, cardiac and plasma MDA levels, but induced mild myocardial fibrosis and significant increase in cardiac GPX activity in comparison with normal rat (p<0.05). However, administration of quercetin or captopril did not ameleriote those mild myocardial fibrosis and increased GPX activity. Uremic cardiomyopathy induced by 5/6 nephrectomy demonstrated mild myocardial fibrosis but preservation of cardiac function demonstrated by NT-proBNP levels. Increased of GPX activity in the nephrectomized-rats compared to the control rats (p<0.05) suggests induction of antioxidant defense mechanisms that might not be exhausted yet. This condition highlighted a compensatory phase which was unchanged following chronic administration of either quercetin or captopril.

Perubahan Parameter Biokimia, Histopatologi Ginjal Tikus Spraque Dawley Pascahipoksia Oleh Ekstrak Akar Acalypha indica dan Herba Centella asiatica

JSFK (Jurnal Sains Farmasi & Klinis) Vol 5, No 3 (2018): J Sains Farm Klin 5(3), Desember 2018
Publisher : Fakultas Farmasi Universitas Andalas

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Abstract

Hipoksia kronik merupakan salah satu penyebab penyakit ginjal akibat peningkatan pembentukan Reactive Oxygen Species (ROS)  dalam sel. Kombinasi ekstrak akar Acalypha indica 250 mg/KgBB (AI250) dan Centella asiatica 150 mg/kgBB (CA150) memiliki efek neuroterapi pada tikus Spraque Dawley pascahipoksia. Penelitian dilakukan untuk membuktikan manfaat kombinasi ekstrak etanol dan/atau ekstrak tunggalnya dapat memperbaiki kerusakan ginjal tikus pascahipoksia melalui mekanisme antioksidan. 28 tikus jantan dikelompokkan dalam 7 kelompok: kontrol normal; kontrol hipoksia+air; hipoksia+(AI200+CA150); hipoksia+(AI250+CA100); hipoksia+AI250; hipoksia+CA150; hipoksia+vitamin C. Hipoksia selama 7 hari dalam hypoxic chamber berisi O2 10% dan N2 90%, 1 atm. Setiap kelompok diberi perlakuan selama 7 hari. Pada akhir studi hewan diterminasi. Darah dan organ ginjal diambil untuk pemeriksaan biokimia dan histopatologi.Kombinasi  (AI250+CA100) menurunkan kadar MDA ginjal dan plasma secara bermakna dibandingkan kontrol hipoksia (p=0,001 dan p=0,021) dan AI250 (p=0,003 dan 0,043). Kombinasi AI250+CA100 terjadi penurunan ekspresi relatif mRNA HIF-1α (p=0,014), kadar urea plasma (p=0,001) dan perbaikan lesi intra-glomerulus p=0,013.Kesimpulan: Kombinasi (AI250+CA100) dan tunggal AI250 memiliki aktivitas antioksidan terbaik dalam mencegah kerusakan ginjal pascahipoksia, secara biokimiawi dan histopatologinya.