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All Journal Jurnal Farmasi Klinik Indonesia INDONESIAN JOURNAL OF PHARMACY JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Science and Technology Indonesia Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) JFIOnline Jurnal Layanan Masyarakat (Journal of Public Service) Jurnal Insan Farmasi Indonesia Prisma Sains: Jurnal Pengkajian Ilmu dan Pembelajaran Matematika dan IPA IKIP Mataram Borneo Journal of Pharmacy Folia Medica Indonesiana
Mahardian Rahmadi
Department Of Clinical Pharmacy, Faculty Of Pharmacy, Airlangga University
Humanities Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Decision Sciences, Operations Research & Management Earth & Planetary Sciences Education Electrical & Electronics Engineering Energy Engineering Environmental Science Health Professions Immunology & microbiology Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Neuroscience Physics Social Sciences Other

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Effect of hydroxyethyl starch 200/0.5 on von willebrand factor serum level and activated partial thromboplastin time (aptt) Atmaja, Sarah Puspita; Khotib, Junaidi; Rahardjo, Eddy; Shinta, Dewi Wara; Rahmadi, Mahardian; Suprapti, Budi
Folia Medica Indonesiana Vol. 51, No. 4
Publisher : Folia Medica Indonesiana

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Abstract

Hydroxyethyl starch (HES) is a colloid administered frequently for intravascular volume expansion during perioperative period. Impairment of haemostasis have been reported during HES administration, but the volume of solution administered was usually higher than 20 ml.kg-1. The objective of this study was to evaluate the effect of Hydroxyethyl starch 200/0.5 dose less than 20 ml.kg-1 on von Willebrand factor serum level and activated partial thromboplastin time. A prospective, observational study was conducted to evaluate von Willebrand factor and activated partial thromboplastin time of patients receiving Hydroxyethyl starch 200/0.5. Inclusion criteria were patients undergoing elective surgery who were going to receive Hydroxyethyl starch 200/0.5 intraoperatively. Fourty six patients were divided into patients receiving crystalloid only group (n=23 patients) and hydroxyethyl starch (n=23 patients). Coagulation variables were assesed 30 minute after insicion and 60 minute after infusion of crystalloid or colloid. Measurement of von Willebrand within each group after crystalloid or HES 200 infusion showed significant decrease, from (mean±SE) 97.688±15.219 ng/ml to 31.611±10.058 ng/ml (p< 0.001) in crystalloid group and 92.884±15.208 ng/ml to 27.378±6.399 ng/ml (p<0.001) in HES 200 group. Activated partial thromboplastin time change was statistically significant (mean±SE) 31.27±1.39 to 35.61±1.62 in HES group only (p=0.007), but this change was not clinically significant. In conclusion, there was neither significant difference in von Willebrand serum level nor in activated partial thromboplastin time between the two groups. There was no coagulation influence with clinically significant effect in the use of HES 20 ml/kg BW in patients undergoing elective surgery.
Neurogenic modulation by neurokinin-1 receptor antagonist, cp-96,345 to inhibit rheumatoid arthritis development in adjuvant induced arthritis rat model Wirasasmita, Yuyun; Rahmadi, Mahardian; Susilo, Imam; Khotib, Junaidi
Folia Medica Indonesiana Vol. 52, No. 2
Publisher : Folia Medica Indonesiana

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Rheumatoid arthritis (RA) is a chronic form of persistent inflammation. Meanwhile, Substance P is the most associated neuropeptide in neurogenic inflammation and hyperalgesia commonly found in chronic pain. Substance P act by binding to neurokinin-1 receptor. The present study was conducted to evaluate the effect of neurokinin-1 receptor antagonist (CP-96,345) on Adjuvant Induced Arthritis rat model, induced by Complete Freund's Adjuvant (CFA). The objective is to attenuate neurogenic inflammation which in turn will increase the latency time of hyperalgesia response, decreases neurokinin-1 receptor expression, and inhibits the development of RA in AIA rat model. Rats were intra-articularly injected with CFA 1 hour after the administration of CP-96,345 either by 0.63 µg/gr; 1.25 µg/gr; or 2.5 µg/gr also intra-articularly. Caliper measurements and hot-plate test were performed on day 0, 3, 5, 7, 9, 11, and day 13. Expression of neurokinin-1 receptor in joint tissue were evaluated by immunohistochemistry, and RA progress in joint tissue were observed hystopathologically. CP-96,345 at 2.5 µg/gr significantly increases the latency of hyperalgesia response time on CFA induced rats (p=0.044) and decreased the neurokinin-1 receptor expression in joint tissue (p=0.029) compared to CFA induced rats. There was no significant difference for caliper measurements and RA progress between CFA incduced rats and treated group. Conclusively, CP-96,345 increases the latency of hyperalgesia response time and decreases the NK-1 receptor expression in rat joint but could not inhibit RA progression.
Development Ischemic Stroke Model by Right Unilateral Common Carotid Artery Occlusion (RUCCAO) Method Mentari, Ika Ayu; Naufalina, Rifda; Rahmadi, Mahardian; Khotib, Junaidi
Folia Medica Indonesiana Vol. 54, No. 3
Publisher : Folia Medica Indonesiana

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This study was designed to examine motor and congnitive changes, infarct lesion and neurohistological changes, involving histologic staining and immunohistochemical expression of caspase-3 after induction by right unilateral common carotid artery occlusion (RUCCAO) for 90 minutes. The animals were divided into two groups: sham group and stroke model group. Cognitive impairment was evaluated by Y maze. Motor function was measured on days 0, 1, 3 and 7 using FUAT paradigm. Infarct area, histological and caspase-3 expressions were evaluated on day 14 after RUCCAO. The results showed that RUCCAO induced cognitive and motor impairment on day 3 and 7. Furthermore, stroke model group induced infarct lesion. Hispatology examination showed body damage of neuron cell in the ipsilateral hemisphere. Moreover, expression of caspase-3 on RUCCAO group was significantly higher than that in sham group. In conclusion, RUCCAO method caused significant cognitive and motor function impairment. Furthermore, RUCCAO also induced infarct lesions and cell death in the thalamus brain area. Thus, RUCCAO can be employed as a method for ischemic stroke model, especially in focal ischemia
The potency of alpha lipoic acid as anti inflammatory on the complete freund's adjuvant-induced rheumatoid arthritis in rat model Megawati, Selvi; Rahmadi, Mahardian; Susilo, Imam; Khotib, Junaidi
Folia Medica Indonesiana Vol. 52, No. 2
Publisher : Folia Medica Indonesiana

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Abstract

Rheumatoid arthritis (RA) is an autoimmune diseases which is characterized by chronic inflammation of the synovial tissue in joints. This research was designed to investigate the effect of alpha lipoic acid as antioxidant on rats with complete freund's adjuvant (CFA)-induced RA by intra articular injection of complete freund's adjuvant (CFA). ALA was administered orally once a day for 7 days at 30, 60 and 120 mg doses a week after CFA injection. The severity of arthritis was evaluated by joint diameter and latency time on thermal stimulation. Joint diameter and latency time on thermal stimulation will measured on day 0, 3, 5, 7, 10, 12 and 14. Measurement of malondialdehyde (MDA) level in plasma was performed using thiobarbituric acid (TBA) method to assess lipid peroxidation. Histology of joint was examined by microscope following hematoxylin-eosin staining. The result showed that treatment with ALA at 30 mg and 60 mg significantly decreased the joint diameter compared to CFA group (p=0.003; p=0.001 respectively) and rat's latency time on thermal stimulation was also significantly increased compared to CFA group (p=0.015; p=0.026 respectively). Measurement of MDA in CFA group and ALA group had no significant difference. Histological staining indicated that the recovery of the synovial membranes of joint in ALA group had no effect. Results indicated that ALA has the effect to suppress the development of inflammation in RA but not through oxidative stress pathway.
Erythropoietin Restores Motor Functions through Angiogenesis in the Thalamus Area of Ischemic Stroke in Rats Lina, Rifda Naufa; Rahmadi, Mahardian; Khotib, Junaidi
Folia Medica Indonesiana Vol. 54, No. 3
Publisher : Folia Medica Indonesiana

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Abstract

The present study aimed to determine the potency of erythropoietin as angiogenesis inducer in ischemic stroke rats model. Animal model was treated by right unilateral common carotid artery occlusion (rUCCAO) for 90 minutes. The stroke model produced decreased motor function. Eight to 12 week-old Wistar rats were used. rHuEPO was administered for 7 days, starting at 24 hours after stroke induction. Motor functions were measured before and 1, 3 and 7 days after rUCCAO. Whereas, histological damage and VEGF expression were evaluated at day 14. The results showed that rHuEPO significantly increased motor function on day 7, reduced the number of damaged body cell and increased VEGF expression in the thalamus area on day 14. As a conclusion, rHuEPO may restore the motoric function and prevent brain neuronal death by inducing angiogenesis through the increase in the expression of VEGF in rUCCAO-induced ischemic stroke model.
The use of hydroxyethyl starch 200/0,5 as plasma subtitutes is safe in hypovolemic patients as indicated in changes of n-acetyl--glucosaminidase and creatinin serum parameters Shinta, Dewi Wara; Khotib, Junaidi; Rahardjo, Eddy; Rahmadi, Mahardian; Suprapti, Budi
Folia Medica Indonesiana Vol. 51, No. 4
Publisher : Folia Medica Indonesiana

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Abstract

Hydroxyethyl Starch (HES) is a compound that improves intravascular volume effectively and rapidly without causing tissue edema. However, HES also has renal safety profile which is still being debated. Based on clinical experience in Dr. Soetomo Hospital, the frequency of acute renal failure following HES 200/0.5 administration at a dose of less than 20 ml/kg (maximum dose) is very rare. The purpose of this study was to evaluate the effect of HES 200/0.5 at a dose of less than 20 ml/kg in patients undergoing surgery. N-acetyl-b-D-Glucosaminidase (NAG) per urine creatinine ratio and creatinine serum were used as main parameter to assess renal injury. This research was observational and prospective design in patients undergoing elective surgery at Gedung Bedah Pusat Terpadu, Dr. Soetomo Hospital, who requiring resuscitation therapy with HES 200/0.5 and met the inclusion and exclusion criteria. NAG was measured prior to surgery and 12 hours after administration of fluid therapy, while creatinine serum was observed before surgery and 48 hours after resuscitation. This study was conducted for three months, and obtained 50 subjects divided into 2 groups, crystalloid group and HES 200/0.5 group. Demographic and baseline characteristics did not differ between groups, except the total bleeding volume. Total bleeding in HES 200/0.5group was higher than crystalloid group (p <0.0001). The mean volume of fluid received in HES 200/0.5 group was 2042.0 ± 673.9 mL, higher when compared with that of crystalloid group (910.0 ± 592.0 ml). Doses of HES 200/0.5 received was 8.31 ± 4.86 ml/kg. Measurement of the of NAG/creatinine ratio and creatinine serum showed significant increase in both groups, but still within the normal range. In addition, the value of these two parameters did not differ between groups. In conclusion, HES 200/0.5 in a dose of less than 20 ml/kg is safe to use in patients who suffered from hypovolemic hemorrhage, without prior history of renal impairment.
Hypoxia-inducible Factor-2α Probably Mediated the Toxicities of Intravenous Beta-Cyclodextrin in Normal and Diabetic Rats’ Kidneys Anita Purnamayanti; Suharjono; Mahardian Rahmadi
JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Vol. 12 No. 3 (2025): JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jfiki.v12i32025.372-381

Abstract

Background: Intravenous β-cyclodextrin administration poses an increased risk of toxicity. Objective: This study aimed to determine the nephrotoxicity of intravenous beta-cyclodextrin (BCD) and its underlying molecular mechanism. Methods: Sixteen Wistar rats were randomly assigned to the healthy or diabetic test group, which received a daily intravenous injection of water for injection or a 6% beta-cyclodextrin solution, respectively, for 28 days. Histopathology was analyzed semi-quantitatively on a 0-5 score basis, and RT-PCR was used to quantify the mRNA expression of HIF-1, HIF-2, IL-1, IL-6, IL-18, and eNOS. Results: There were no deaths in any of the groups, and renal function declined in the test groups. Histopathological findings revealed abnormalities in vascular integrity, cellular infiltration/damage, and necrosis in the kidney, while the relative expression of mRNA for hypoxia-inducible factors (HIFs), a marker of regional renal hypoxia, was upregulated. Conclusion:  Intravenous administration of beta-cyclodextrin increases the risk of nephrotoxicity, and the molecular mechanisms underlying kidney injury are probably mediated by hypoxia inducible factors-2α (HIF-2α). We strongly suggest that future research should be conducted with an adequate sample size.
Characteristics, Release, and Stability (Kinetics and Shelf-life) of Ciprofloxacin HCl-Alginate-Carrageenan Microspheres: Effects of Drug Concentration and Type of Lyoprotectant Amiruddin; Rahmadi, Mahardian; Hariyadi, Dewi Melani
Science and Technology Indonesia Vol. 11 No. 1 (2026): January
Publisher : Research Center of Inorganic Materials and Coordination Complexes, FMIPA Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.26554/sti.2026.11.1.148-160

Abstract

Tuberculosis, an infectious disease caused by the Mycobacterium tuberculosis bacteria, is one of the main causes of death worldwide. Alternative treatments are necessary due to the rising prevalence of medication resistance in Mycobacterium tuberculosis. Fluoroquinolones, such as ciprofloxacin HCl, are among these alternatives and are generally administered orally, but they have limitations. Therefore, pulmonary targeted inhalation delivery systems have been developed. Inhalation of microspheres enables deposition in the lungs at appropriate particle sizes. This study formulates ciprofloxacin HCl microspheres with an optimal ratio and concentration of polymer combination and crosslinker, aiming to determine the effect of drug concentration and lyoprotectant type on characteristics, release, and stability, including degradation kinetics and shelf life. The results showed that the ciprofloxacin HCl-alginate-carrageenan microsphere powder was yellowish-white, with smooth morphology, a yield percentage of 96.08% ± 0.84 – 97.00% ± 0.19, particle sizes below 5 µm, drug loading between 4.57% ± 0.13 – 6.76% ± 0.06, and entrapment efficiency ranging from 79.45% ± 2.53 – 90.80% ± 0.77. The powder had moisture content below 5% and excellent flow properties. Ciprofloxacin HCl release from microspheres at pH 7.4 for 30 hours was 84.55% ± 0.89 – 90.74% ± 0.22, following Korsmeyer-Peppas kinetics based on the Fickian diffusion mechanism. Ciprofloxacin HCl-alginate-carrageenan microspheres were stable and exhibited good shelf life. This study concluded that particle size, drug loading, entrapment efficiency, and drug release are all influenced by drug concentration, while moisture content and flow properties, with adequate shelf life, are influenced by the type of lyoprotectant.
Optimization of ADMET Properties Prediction for Remdesivir, Favipiravir, and their Metabolites Elimination Profiles Purnamayanti, Anita; Suharjono, Suharjono; Rahmadi, Mahardian
Borneo Journal of Pharmacy Vol. 9 No. 1 (2026): Borneo Journal of Pharmacy
Publisher : Institute for Research and Community Services Universitas Muhammadiyah Palangkaraya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33084/bjop.v9i1.8464

Abstract

In silico methods have become crucial for the rapid preliminary assessment of drug compound absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, particularly for vital antivirals such as remdesivir and favipiravir, early in the drug development process. This study aimed to predict the pharmacokinetic profiles of remdesivir, favipiravir, and their respective metabolites, explicitly focusing on their interactions within the unique anatomy and physiology of human elimination organs. Compound summaries from PubChem were computationally analyzed using the pkCSM, ProTox-II, and ADMETLab 3.0 platforms. These predictions were then critically evaluated in the context of established hepatic and renal elimination mechanisms. Favipiravir and its metabolites generally exhibited a favorable ADMET profile, characterized by good oral absorption, wide distribution, efficient metabolism, and rapid excretion, albeit with a slight potential for blood-brain barrier penetration. In contrast, remdesivir, its nucleotide metabolite, and favipiravir showed the highest predicted likelihood of inducing hepatotoxicity. Concerning renal toxicity, remdesivir, remdesivir monophosphate, and the active triphosphate forms of both remdesivir and favipiravir presented a notable risk. This elevated renal risk was primarily attributed to their predicted low renal clearances, potentially resulting from insufficient penetration across the negatively charged glomerular filtration barrier. In conclusion, favipiravir and its metabolites demonstrated a more desirable ADMET profile than remdesivir. These preliminary findings suggest a differential safety and pharmacokinetic landscape between the two antiviral agents. Future research should prioritize leveraging advanced AI-based ADMET platforms to simulate complex human organ functions more accurately, refining these predictive models, and guiding subsequent in vivo investigations.
Co-Authors Abdul Rahem, Abdul Alma Nuril Aliyah Amiruddin Ana Yuda Anak Agung Sagung Dyah Pramesti Andarsari, Mareta R. Aniek S. Budiatin Anita Purnamayanti Aprilia, Pingkan Aqsha, Aulia Charis Arie Sulistyarini Arina Dery Puspitasari Bambang Sidharta Budi Suprapti Budiatin, Aniek S. Budiatin, Aniek Setiya Budiatin, Aniek Setiya Budiatin, Aniek Setya Budiatin, Aniek Setya Cahyo Wibisono Chris Alderman Chrismawan Ardianto Chrismawan Ardianto Dewi Melani Hariyadi Dewi W. Shinta Dewi Wara Shinta Didik Hasmono Eddy Rahardjo Farida Ifadotunnikmah Fathia Ramadiani Galuh Laksatrisna Pide Gesnita Nugraheni Gusti Noorrizka Veronika Ahmad Hapsari, Pharmasinta P. Hermansyah, Andi Heru Purwanto I Nengah Budi Sumartha I NYOMAN WIJAYA Ika Ayu Mentari Imam Susilo Indira D. Kharismawati Irvina Harini Junaidi Khotib Liempepas, Angelika Lina, Rifda Naufa Luke Wongso Mareta R. Andarsari Mareta Rindang Andarsari Megawati, Selvi Muhammad Agus Syamsur Rijal Muhammad Taher Muhammad Zaki Bin Ramli Naufalina, Rifda Nia Widyasari Noorma Rosita Pharmasinta P. Hapsari Pingkan Aprilia Priyandani, Yuni Rahman, Fakhrinnisa Wildani Ramadiani, Fathia Rifda Naufa Lina Rifda Naufalina Sairiyah, Siti Nasikatus Samirah Samirah Sarah Puspita Atmaja Shinta, Dewi W. Sjamsiah, Siti Sjamsiah, Siti Suharjono Suharjono, Suharjono Sukorini, Anila Impian Sumarno . Sumarno Sumarno Sumartha, I Nengah Budi Tarisya Dinda Saraya Toetik Aryani Tuhfatul Ulya Umi Athiyah, Umi Winda Fatma Sari Wirasasmita, Yuyun Yulistiani Yulistiani Yulistiani, . Yusuf Alif Pratama Zainul Amiruddin Zakaria Zamrotul Izzah Zulkarnain, Bambang Subakti