Franciscus D. Suyatna
Department of Pharmacology, Faculty of Medicine, Universitas Indonesia

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Interaction of erythromycin and clarithromycin with orange juice Setiawati, Arini; Wiria, Metta S.S.; Suyatna, Franciscus D.; Sion, Juan T.; Hamadian, Marina
Medical Journal of Indonesia Vol 14, No 2 (2005): April-June
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (284.902 KB) | DOI: 10.13181/mji.v14i2.573


Concomitant administration of orange juice with fexofenadine has been found to decrease the bioavailability of fenofenadine to less than 30% via inhibition of organic-anion transporting polypeptide (OATP), a drug uptake transporter expressed in organs such as liver, kidney and intestine. Erythromycin and clarithromycin are substrates and inhibitors of CYP3A4, a drug metabolizing enzyme in the liver and enterocytes, and P-glycoprotein (P-gp), a drug efflux transporter expressed in the same organs as OATP. Since an extensive overlap exists between substrates and inhibitors of CYP3A4, P-gp and OATP transporters, we want to study the effect of coadministration of our local orange (Siam orange) juice on the bioavailability of the above antibacterials. We conducted two 2-way cross-over randomized studies, one study for each antibacterial (500 mg), crossed between administration with orange juice (200 ml) and with water, in 12-13 healthy subjects per study. The serum concentrations of the antibacterials were assayed by microbiological method. The mean (range) ratio of AUC0-t with orange juice/with water were as follows : erythromycin : total (n=13) 81.7 (9.7-193.8)%, unchanged (n=4) 96.4 (80.5-107.9)%, decreased (n=6) 31.9 (9.7-49.0)%, increased (n=3) 161.8 (134.6-193.8)%; clarithromycin : total (n=12) 91.4 (20.6-158.3)%, unchanged (n=5) 103.1 (80.9-123.0)%, decreased (n=4) 34.8 (20.6-64.3)%, increased (n=3) 147.2 (132.9-158.3)%. It was concluded that coadministration of Siam orange juice with erythromycin or clarithromycin produced unpredictable effects on the bioavailability of these antibacterials in individual subjects, with marked decreases in almost half of the subjects, although in totals the effects were not statistically significant. (Med J Indones 2005; 14: 78-86)Keywords: interaction, erythromycin, clarithromycin, orange juice.
Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture Iskandarmudasyah, Adam; Louisa, Melva; Arleni, Arleni; Jusman, Sri W.A.; Suyatna, Franciscus D.
Medical Journal of Indonesia Vol 21, No 1 (2012): February
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (358.898 KB) | DOI: 10.13181/mji.v21i1.471


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
Effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress Victor, Andi A.; Gondhowiardjo, Tjahjono D.; Waspadji, Sarwono; Wanandi, Septelia I.; Bachtiar, Adang; Suyatna, Franciscus D.; Muhiddin, Habibah
Medical Journal of Indonesia Vol 23, No 2 (2014): May
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (545.754 KB) | DOI: 10.13181/mji.v23i2.756


Background: This study was aimed to compare the effect of laser photocoagulation (LF), intravitreal bevacizumab (IVB) and combined treatments on biomarkers of oxidative stress such as aldehhyde dehidrogenase (ALDH), malondialdehyde (MDA) level, superoxide dismutase (SOD) activities, and vitreal vascular endothelial growth factor (VEGF) on proliferative diabetic retinopathy (DR) patients.Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital between February 2011 - June 2013 were randomized into 4 groups : 1) control (n = 18); 2) LF pre-vitrectomy (n = 18); 3) IVB pre-vitrectomy (n = 18); and 4) combined IVB and LF pre-vitrectomy (n = 18). One-way ANOVA was used to compare oxidative stress parameters in the four groups.Results: There were no statistically significant differences in the average plasma ALDH activity (0.034 ± 0.02; 0.027 ± 0.02; 0.025 ± 0.02; 0.031 ± 0.11 IU/mg protein; p = 0.66), vitreal MDA level (1.661 ± 1.21; 1.557 ± 1.32; 1.717 ± 1.54; 1.501 ± 1.09 nmol/mL; p = 0.96) and SOD activity) (0.403 ± 0.50; 0.210 ± 0.18; 0.399 ± 0.49; 0.273 ± 0.32 U/mL; p = 0.38) among these four groups, respectively. However, the VEGF vitreal level (pg/mL) showed a statistically significant difference (0.356 ± 0.60; 0.393 ± 0.45; 0.150 ± 0.24; 0.069 ± 0.13; p = 0.05). The VEGF level in combination group was five times lower than the control group (p = 0.05).Conclusion: Combined treatments of DR by IVB and LF were correlated with lower vitreal MDA and plasma VEGF level, but did not have any effect on plasma ALDH and vitreal SOD in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients.  
F2α-isoprostane, Na+-K+ ATPase and membrane fluidity of placental syncytiotrophoblast cell in preeclamptic women with vitamin E supplementation Rusdi, Rusdi; Soeradi, Oentoeng; Subakir, Sri B.; Suyatna, Franciscus D.
Medical Journal of Indonesia Vol 21, No 4 (2012): November
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (429.077 KB) | DOI: 10.13181/mji.v21i4.510


Background: The aim of our study was to analyze F2α-isoprostane level, Na+-K+ ATPase activity and placental syncytiotrophoblast cell membrane fluidity in preeclamptic women who received vitamin E supplementation.Methods: The study was conducted between September 2003 and February 2005 at Budi Kemuliaan Maternity Hospital, Central Jakarta. Samples were 6 preeclamptic women with vitamin E supplementation, 6 preeclamptic women without vitamin E supplementation and 6 normal pregnant women. The dose of vitamin E was 200 mg daily. F2α-isoprostane was measured with ELISA reader at λ of 450 nm. Cell membrane fluidity was measured by comparing the molar ratio of total cholesterol and cell membrane phospholipid concentration. The cholesterol was measured by Modular C800 using Roche reagent. Phospholipid was measured by Shimadzu RF5301PC spectrofluorometer (excitation 267 nm, emission 307 nm). Na+-K+ ATPase activity was inhibited by ouabain. Pi production was measured with Fiske and Subbarow method using spectrophotometer at λ of 660 nm. Data was analyzed using F test with one-way ANOVA.Results: Vitamin E supplementation in preeclamptic women decreased the oxidative stress, indicated by significantly lower level of F2α-isoprostane compared to those without vitamin E (26.72 ± 11.21 vs 41.85 ± 7.09 ng/mL, respectively, p = 0.017). Membrane fluidity in syncytiotrophoblast cell of preeclampsia with vitamin E group was maintained at 0.39 ± 0.08 while in those without vitamin E was 0.53 ± 0.14 (p = 0.04). Na+-K+ ATPase activity in syncytiotrophoblast cell membrane was not affected by vitamin E (p = 0.915).Conclusion: Vitamin E supplementation in preeclamptic women decreases F2α-isoprostane level and maintains cell membrane fluidity of syncytiotrophoblast cells; however, it does not increase Na+-K+ ATPase enzyme activity. (Med J Indones. 2012;21:225-9)Keywords: F2α-isoprostane, membrane fluidity, Na+-K+ ATPase, preeclampsia, vitamin E
Cytoglobin expression in oxidative stressed liver during systemic chronic normobaric hypoxia and relation with HIF-1α Jusman, Sri W.A.; Iswanti, Febriana C.; Suyatna, Franciscus D.; Ferdinal, Frans; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 23, No 3 (2014): August
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (412.573 KB) | DOI: 10.13181/mji.v23i3.1025


Background: Liver is sensitive against hypoxia and hypoxia will stabilize HIF-1α. At the same time, hypoxia will produce reactive oxygen species (ROS) which can be scavenged by Cygb. The purpose of our study is to know, if normobaric hypoxia can induce Cygb expression and its association with HIF-1α stabilization.Methods: This is an experimental study using 28 male Sprague-Dawley rats, 150-200 g weight. Rats are divided into 7 groups: control group and treatment groups that are kept in hypoxic chamber (10% O2: 90% N2) for 6 hours, 1, 2, 3, 7 and 14 days. All rats are euthanized after treatment and liver tissue are isolated, homogenized and analyzed for oxidative stress parameter, expression of Cygb and HIF-1α.Results: Expression of Cygb mRNA and protein was increased on the day-1 after treatment and reach the maximum expression on the day-2 of hypoxia treatment. But, the expression was decreased after the day-3 and slightly increased at the day-14 of hypoxia. The correlation between expression of Cygb and oxidative stress parameter was strongly correlated. Cygb mRNA, as well as protein, showed the same kinetic as the HIF-1, all increased about day-1 and day-2.Conclusion: Systemic chronic hypoxia and/or oxidative stress up-regulated HIF-1α mRNA which is correlated with the Cygb mRNA and protein expression. Cygb mRNA as well as Cygb protein showed the same kinetic as the HIF-1, all increased about day-1 and day-2 suggesting that Cygb could be under the regulation of HIF-1, but could be controlled also by other factor than HIF-1.
The Improving of Methylprednisolone Palmitate Potency After Incorporated With Liposome - an Antiinflammation Study In Culture of Mice’s Splenocytes Wawaimuli Arozal; Franciscus Dhyanagiri Suyatna; Ernie Hernawati Purwaningsih; Hedi R. Dewoto
Makara Journal of Health Research Vol 9, No 2 (2005): December
Publisher : Universitas Indonesia

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Glucocorticoid has been used as an antiinflammatory and immuno-suppresive drug. Longterm utilisation at high dose of glucocorticoid is associated with serious side effects. In recent years, many attempts have been performed in searching the appropiate vehicles to deliver the drug directly into the target organ or the receptor. By incorporating the drug into its vehicle such as liposome, the systemic side effect can be minimized. Purwaningsih et al has successfully synthetized a novel preparation of liposome methylprednisolone palmitate (L-MPLP). The aim of the study was to learn the pharmacological effect of L-MPLP, especially on antiinflammatory effect of this novel preparation, compared with the standard methylprednisolone (MPL). The parameter was the potency of L-MPLP in reducing gamma-interferon production in T-lymphocyte culture after stimulation with concanavalin A in vitro as well as in vivo. Gamma-interferon was assayed by ELISA method. The reduction of gamma interferon, in vivo, after the administration of L-MPLP at the dose of 2,8 and 16 mg/kgBW respectively, showed significant difference than a control group, while MPL did not. The addition of both L-MPLP and MPL in in vitro culture at the concentration of 5.10-3, 5.10-2 and 5.10-1 mM have proved to suppress the gammainterferon production, where the suppression of L-MPLP was more effective than MPL, significantly.
The effects of Curcuma against paracetamol-induced liver damage in rats Suyatna, Franciscus D; Gan, Sulistia; Siswoyo, Koesparti; Asikin, Nur; Rosmiati, Hedi; Pringgoutomo, Sudarto
Medical Journal of Indonesia Vol 1, No 1 (1992): January-March
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (3051.049 KB) | DOI: 10.13181/mji.v1i1.3522


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