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Journal : INDONESIAN JOURNAL OF PHARMACY

SYNTHESIS AND ANALGETIC ACTIVITY EVALUATION OF 4-[N-(4-HYDROXYPHENYL)CARBOXYMIDOYL]-2-METHOXYPHENOL Pudjono, Pudjono; Anindita, Jessica; Hakim, Arief Rahman; Purnomo, Hari
INDONESIAN JOURNAL OF PHARMACY Vol 27 No 2, 2016
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (627.434 KB) | DOI: 10.14499/indonesianjpharm27iss2pp99

Abstract

Paracetamol is an analgesic-antipyretic compound derived from p-aminophenol. Though paracetamol has good efficacy and safety on consumption, parasetamol has hepatotoxic effect as its     adverse drug reaction. 4-[N-(4-hydroxyphenyl)carboxymidoyl]-2-methoxyphenol is one of p-aminophenol derivative that was already been determined in silico using molecular docking PLANTS method, and it was known that 4-[N-(4-hydroxyphenyl) carboxymidoyl]-2-methoxyphenol has analgesic effects more potent and has hepatotoxic adverse effect lower than paracetamol. 4-[N-(4-hydroxyphenyl)carboxymidoyl]-2-methoxy-phenol can be synthesized through reaction of p-aminophenol with vanillin under acid condition. The synthesized products were recrytalized, dried, and the purity was determined with melting point determination and Thin Layer Chromatography. The structure of pure crystals were elucidated using IR, 1H-NMR, C-NMR, and Mass Spectroscopy. The analgesic evaluation was carried in vivo using writhing test method. The synthesized compound were divided into three dosage variations, 0,5; 1; and 2 mol equivalent to 100 mg/kgBB of paracetamol (reference drug). 4-[N-(4-hydroxyphenyl)carboxymidoyl]-2-methoxyphenol with 1 mol dosage has analgesic activity better than paracetamol but the difference was not significant.Keywords: 4-[N-(4-hydroxyphenyl)carboxymidoyl]-2-methoxyphenol, p-aminophenol, analgesic, writhing test
EFFECT OF PENTAGAMAVUNON-0 TO THE THEOPHYLLINE PHARMACOKINETICS IN RATS Hakim, Arief Rahman; Hakim, Lukman; Margono, Supardjan A.
Indonesian Journal of Pharmacy Vol 14 No 1, 2003
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (97.087 KB) | DOI: 10.14499/indonesianjpharm0iss0pp244-249

Abstract

The research was aimed to observe pentagamavunon-0 activities to theophylline pharmacokinetics in rats. The study of interaction pentagamavunon-0 and theophylline was conducted employing a completely randomized design using male Wistar rats which were divided into 5 groups (6 rats for each group). The groups were given a single oral theophylline 25 mg/kg BW as a control group and were administered single oral pentagamavunon-0 2, 5, 10 and 40 mg/kg BW each dose 4 hours before treatment with theophylline. Serial blood samples (0,2 ml) were withdrawn at various interval via the tail vein for HPLC analysis of unchanged theophylline in blood. The concentration of theophylline was determined based on a standard curve. The concentration-time data determines theophylline pharmacokinetics i.e. Ka, Cmaks, tmaks, AUC0-, Vdss, t1/2 elimination, Clt and MRT. The results indicated that pentagamavunon-0 was found to be able to decrease theophylline clearance 40-51% (P<0.05). The decrease in clearance causes the prolonged life of theophylline in the body.Key words : Pentagamavunon-0, Theophylline, Pharmacokinetics
Effect of the curcuma plus® syrup on the pharmacokinetics of rifampicin in rats Wahyono, Djoko; Hakim, Arief Rahman; ., Purwantiningsih
Indonesian Journal of Pharmacy Vol 18 No 4, 2007
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (201.119 KB) | DOI: 10.14499/indonesianjpharm0iss0pp163-168

Abstract

The research was aimed to observe the effect of Curcuma plus® syrup on rifampicin pharmacokinetics in rats.The study of interaction Curcuma plus® syrup with rifampicin pharmacokinetics was conducted employing a completely randomized design using male Sprague Dawley rats which were divided into 3 groups (5 rats for each group). The groups were given a single oral rifampicin dose of 50 mg/kg BW as a control group and were confered single oral Curcuma plus syrup 2.7 mL/kg BW one hour before rifampicin and daily dose for 7 days, then is given rifampicin after that. Serial blood samples (0,2 mL) were withdrawn at various interval via the vein for HPLC analysis of unchanged rifampicin in blood. The concentration of rifampicin was determined based on a standard curve, and from the concentration to time data was determined rifampicin pharmacokinetic parameters (Cmaks, tmaks, AUC0-∼, Vd/F, t1/2, ClT dan K).The results indicated that Curcuma plus® syrup single dose 2.7 mL/kg BW one hour before rifampicin could increased rifampicin volume of distribution by 225.80% (P<0.05) and caused decreased Cmaks 72.81% and AUC0-inf 63.93% (P<0.05), while daily dose Curcuma plus® syrup for 7 days could rise rifampicin total clearance 225.60% (P<0.05) and caused decrease by 76.94% of AUC0-inf (P<0.05).Key words : pharmacokinetics, Curcuma plus® syrup, rifampicin
A BIOAVAILABILITY STUDY OF INDONESIAN GENERIC TABLET OF CAPTOPRIL IN HEALTHY VOLUNTEERS Nugroho, Agung Endro; Hakim, Arief Rahman; ., Purwantiningsih; Hakim, Lukman
Indonesian Journal of Pharmacy Vol 23 No 3, 2012
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (691.336 KB) | DOI: 10.14499/indonesianjpharm23iss3pp183-187

Abstract

Captopril  is  a  selective  inhibitor  of  angiotensin-converting enzyme  (ACE)  and  is  formulated  by  several  pharmaceutical companies in Indonesia. This study was conducted to compare the bioavailability  of  a  captopril  tablet  with  reference  products  in healthy  volunteers.  The  relative  bioavailability  of  captopril  was determined in single dose, randomized, crossover,  and  two-phase studies.  The  relative  bioavailability  of  the  test  product  (a  generic captopril 50 mg tablet) with respect to the reference product was determined. Twelve healthy volunteers in two groups took part in these  studies  and  took  either  the  test  or  reference  tablets  in  the first  phase  and  received  the  other  tablet  in  the  second  phase  of each  study.  The  bioavailability  parameters  include  the  peak concentration  of  captopril  in  serum  (Cmax);  the  time  to  achieve the  peak  concentration  (Tmax);  and  the  area  under  the  curve  of captopril  in  serum  versus  time.  Non-compartmental  analysis  on observed concentration versus time data has resulted in the mean value of Cmax of 545.26 ± 22.90 ng/mL (test product) and 548.91 ± 25.07 ng/mL (reference product) and mean Tmax of 1.13 ± 0.08 hours  (test  product)  and  1.08  ± 0.08  hours  (reference  product), mean  of  AUC0-7  value  of  1820.51  ± 75.31  ng.  hour/mL  (test product)  and  1822.09  ± 99.29  ng.  hour/mL  (reference  product), and  mean  of  AUC0-inf  value  of 1967.83  ±  95.65  ng. hour/mL  (test product)  and  1996.94  ± 124.52  ng.  hour/mL  (reference  product). Based on the data, it can be concluded that there is no significant difference  (p>0.05)  in  bioavailability  between  both  captopril Tablet (test and reference product).Key words: Bioequivalence, Captopril, HPLC, Human serum, Generic 
The effect of pentagamavunon-0 pretreatment to the pharmacokinetic of paracetamol profile on wistar male rats Wahyono, Djoko; Hakim, Arief Rahman
Indonesian Journal of Pharmacy Vol 17 No 4, 2006
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (194.142 KB) | DOI: 10.14499/indonesianjpharm0iss0pp194-198

Abstract

Drug interaction can happen when two or more drugs are given together. This research was aimed to observe the effect of PGV-0 pretreatment to paracetamol pharmacokinetic profile in male rats.The study was conducted employing a one-way randomized completely design, using male Wistar rats weight 150 g (±10%). The animals were divided into three groups (5 rats for each group). Group I (control) was given a single oral paracetamol 150 mg/kg BW. The other groups II dan III were given a single oral PGV-0 20 and 40 mg/kg BW one hour before treatment with paracetamol respectively. After all rats were pretreated, serial blood and urine samples were withdrawn and were analysed using HPLC for unchanged paracetamol. Pharmacokinetic parameters of paracetamol i.e. Cmax, tmax, AUC, K, t1/2, Vdss/F, Cl/F, Aecum, dan %fe were determined based on concentration to time data in the blood and urine. The paracetamol pharmacokinetic parameters were analyzed by one-way analysis of varians (ANOVA) using 95% confidence interval. And the difference between groups were analyzed using Tukey-test method. The results showed that the pharmacokinetic parameters of paracetamol in the animals prefed with PGV-0 20 and 40 mg/kg BW did not change significantly (P > 0.05).Key words : pharmacokinetics, interaction, paracetamol, Pentagamavunon-0
Population-Based Approach to Analyze Sparse Sampling Data in Biopharmaceutics and Pharmacokinetics using Monolix and NONMEM Akhmad Kharis Nugroho; Arief Rahman Hakim; Lukman Hakim
Indonesian Journal of Pharmacy Vol 28 No 4, 2017
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1378.459 KB) | DOI: 10.14499/indonesianjpharm28iss4pp205

Abstract

Although it has been developed since 1972, the implementation of a population-based modeling approach in Indonesia, particularly to analyze biopharmaceutics and pharmacokinetics data is still very limited. This study was aimed to evaluate the performance of Monolix and NONMEM, two of the popular software packages in a population-based modeling approach, to analyze the limited data (sparse sampling data) of the time profiles of the simulated plasma drug concentration of a theoretical compound. and NONMEM were used to model the limited data (40 data points) as a results of the random selection from the 180 point data of simulated plasma drug concentration (Cp) on 20 subjects at 0.25; 0.5; 0.75; 1; 1.5; 3; 6; 12 and 18 hours after per-oral administration of a 100mg of a theoretical compound. Population values of the absorption rate constant (Ka), the elimination rate constant (Kel) and volume of distribution (Vd) were compared to the average Ka, Kel and Vd obtained by the conventional method (two stage approach) using PKSolver on the Cp data of all subjects. The calculation system of a nonlinear mixed effect model in Monolix and NONMEM, successfully describes the sparse data, based on the visual evaluation of the goodness of fit. Comparison of parameter estimates of population values in Monolix and NONMEM are in the range of 94 to 108% of the real values of the rich data analysed by PKSolver. A population-based modeling can adequately analyze limited or sparse data, demonstrating its capability as an important tool in clinical studies, involving patients.
Pharmacokinetics profile of pentagamavunon-0 after potassium pentagamavunonat-0 oral administration in rats Arief Rahman Hakim; Agung Endro Nugroho; Lukman Hakim
Indonesian Journal of Pharmacy Vol 17 No 4, 2006
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (201.544 KB) | DOI: 10.14499/indonesianjpharm0iss0pp204-211

Abstract

Potassium PGV-0 was a salt form of PGV-0 which has been developed to be a new medicine. The salt form was relatively water soluble and therefore was is expected to have better bioavailability and efficacy than the parent compound.The research aims were to investigate the pharmacokinetics profiles of PGV-0 after the administration of its potassium salt per orally in male rats Wistar The treadment was done by using a completely randomized design to explore the profiles of PGV-0 in blood, its distribution into primary organs : liver, kidneys, lungs and small intestine, and also its elimination into urine and feces in the animals. Potassium PGV-0 was given single doses per orally at 40 and 80 mg/kg BW. The analytical assay for PGV-0 was conducted by an HPLC method with a UV-Vis detector.The results shown that according to per oral administration of K-PGV-0 to the rats, there was no PGV-0 found in the blood monitored up to 360 minutes. The compound was not found in the liver nor kidneys, and only traces (<5% of dose) were found in the lungs or small intestine. Traces amounts of PGV-0 were also found in urine or feces. The extremely rapid disappearance of the compound from the blood may not be due to its rapid distribution into the organs but more likely due to its fast biotransformation in the blood or in the liver. This assumption is also supported by the facts that PGV-0 found in the urine or feces was negligible (< 5% of administered dose).Key words : potassium pentagamavunon-0, pentagamavunon-0, pharmacokinetics
The effect of betle (Piper betle L.) leaf juice pretreatment on the pharmacokinetics of propranolol on male white rat Agung Endro Nugroho; Arief Rahman Hakim
Indonesian Journal of Pharmacy Vol 14 No 4, 2003
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (307.452 KB) | DOI: 10.14499/indonesianjpharm0iss0pp169-176

Abstract

Drug interaction phenomenon, between drugs on drug and ford (fruit, vegetables on others), can happen in drug therapy of a disease due to the existence of compounds other than the drug (fruits, vegetables or drink). This interaction can alter and affect the action and effect of the drug. The aim of the research is to study an interaction between betle leaf (a vegetable ) and propranolol, which is a beta-blocker with a high hepatic extraction ratio, in male white rat. The study was conducted by employing a completely randomized design in male wistar inbreed rat (aged 2-2.5 months, 150-250 g). The animals in group I were given propranolol with an oral single dose of 7.5 mg/kg BW (control group) and in group II were given pretreatment with betle leaf juice dose of 17 mL/kg BW at an hour prior propranolol administration. After collected at some certain times, the drug concentration on bloods were analyzed with a Spectropflurometer.The results shown that pretreatment of betle leaf juice did not affect the absorption rate constant (Ka) significantly (P>0.05), and increase the total clearence (ClT) and volume of distribution in steady state (Vdss) significantly (P<0.05). The increasing of both ClT and Vdss caused alteration of the secondary pharmacokinetics parameters of propranolol and these derivates significantly(P<0.05) except the mean residence time value (MRT). This it is concluded that the pretreatment of betle leaf juice with the dose of 17 mL/kg BW affect the pharmacokinetics of propranolol or decrease the propranolol concentration in blood.Key words : propranolol, betle leaf, pharmacokinetics and drug interaction
Feasibility of transdermal transport of atenolol by combination of iontophoresis and oleic acid pretreatment Akhmad Kharis Nugroho; Arief Rahman Hakim; Marlyn Dian Laksitorini; Fajar Rakhmatullah; Eny Masruriati
Indonesian Journal of Pharmacy Vol 22 No 1, 2011
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (400.814 KB) | DOI: 10.14499/indonesianjpharm0iss0pp65-72

Abstract

Atenolol  has  a  low  oral  bioavailability  and  a  short  elimination  half-life. Therefore,  alternative  route  and  delivery  system  is  important.  Transdermal iontophoresis,  i.e.  a  systemic  drug  delivery  via  the  skin,  implementing  a  low intensity  of  electrical  current,  is  one  attractive  candidate.  This  study  evalu ated feasibility  of  atenolol  transdermal  transport  when  iontophoresis  is  applied  after enhancer  pretreatment.  There  were  4  formulas  prepared;  2  implemented iontophoresis  for  3  hours  (current  density:  0.25  mA/cm2)  while  the  others  did not  use  iontophoresis.  The  enhancer  was  oleic  acid  (5  or  10%  as  a  mixture  in propylene  glycol)  with  duration  of  pretreatment  of  one  hour.  Transport  was evaluated  in  the  diffusion  studies  across  the  fresh  rat  skin  in  a  static-vertical diffusion system. Data were analyzed based on the numeric convolution method to  obtain  simulated  Cp  profiles  as  well  as  AUC  of  Cp  profiles.  Based  on  the simulated Cp, the best transport was achieved in Formula 3, where iontophoresis is  performed  across  the  skin,  pretreated  with  5%  oleic  acid  for  one   hour.  The value  of  simulated  Cp  indicated  achievement  of  therapeutics  level  of  atenolol, suggesting the feasibility of the atenolol delivery by iontophoresis.Key words : atenolol, transdermal, iontophoresis, enhancer
Profile of sulphacetamide pharmacokinetics on uranyl nitrate-induced renal failure rats Djoko Wahyono; Arief Rahman Hakim; Agung Endro Nugroho
Indonesian Journal of Pharmacy Vol 18 No 3, 2007
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (180.141 KB) | DOI: 10.14499/indonesianjpharm0iss0pp117-123

Abstract

Kidney is a vital organ which has main function to maintain the body homeostasis. The role of kidney is the excretion (elimination) of waste product, and if there is pathologically a renal failure so will change the drug pharmacokinetics and in turn change it’s potency. The present study evaluated the effect of uranyl nitrate-induced renal failure on the pharmacokinetics profiles of sulphacetamide in rats.The study was conducted by employing a completely randomized design in male Wistar in bred rat (aged 2-2.5 months, 150-250 g). The animals in group I were given sulphacetamide sodium with an oral single dose 100.0 mg/kg BW (control group) and in group II were given pretreatment with uranyl nitrate at 3 days before sulphacetamide administration.After collected at some certain times, the drug concentrations on bloods were analyzed by an ultraviolet spectrophometer. The results have shown that uranyl nitrate-induced renal failure decreased the primer pharmacokinetics parameter i.e. total clearance (ClT) and volume of distribution in steady state (Vdss), significantly (P<0.05). The decreasing of these parameter could cause alteration of the secondary pharmacokinetics parameters of sulphacetamide and these derivates i.e. Cmax, tmax, AUC0-240, AUC0-inf, MRT, K and t1/2 elimination significantly (P<0.05). According from the results, it is concluded that uranyl nitrate-induced renal failure affected the pharmacokinetics of sulphacetamide or could increase the sulphacetamide concentration in blood.Key words : sulphacetamide, pharmacokinetics, renal failure, uranyl nitrate
Co-Authors ., Purwantiningsih ., Purwantiningsih A.A. Ketut Agung Cahyawan W Abadi Sanosra Afitri, Windy Dwi Agung Endro Nugroho Agung Endro Nugroho Agung Endro Nugroho Agung Endro Nugroho Ahmad Syukri Aji Jumiono Akhmad Kharis Nugroho Akhmad Syarif Alva Hendi Muhammad Ananda , Dhimas Aryo Vipha Andi Cudai Nur ANDIKA GUTAMA, ANDIKA Anindita, Jessica Anjarwati Anjarwati Arief Nurrochmad Asro Laelani Indrayanti Astini, Siluh Made Yuni Auliana, Diah Fitrotul bin Yahaya, Mohd Firdaus Br Tarigan, Maya Sari Butarbutar, Maria Haryanti Chaerani, Ika Tania Cicilia Ika Rahayu Nita Daeli, Abiyudin Dedy Suryadi Diana, Ratna Dion Notario Djoko Wahyono Djoko Wahyono Djoko Wahyono Dwi Agus Setiawan DWI CAHYONO dwi yasa, arnelia Edy Budi Harjono, Edy Budi Edy Meiyanto Endang Lukitaningsih Eny Masruriati Eny Susilowati Evradus Badii Fadhil Hasan R, Hans Mokhammad Fadhli, Khairul Fajar Rakhmatullah Faradilla, Aina Noor Ade Farida Nur Kumala Fathul Jannah Fauzi, Soni Fotriyodi, Rivon Gunawan Prayitno Haedar Akib Hakim, Lukman Hakim, Lukman Harefa, Sepakat Jaya HARI PURNOMO Hariani, Pipit Putri Harry Nenobais Haryadi, Nicko Haryanti Butarbutar, Maria Hasibuan, Ahmad Riady Hasibuan, Bulkis Hayati, Farida Helmi Haris Heris Yosua Ramase Rony Hulu, Safira Ida Ayu Putu Sri Widnyani Idsan, Rakha Satya Imono Argo Donatus, Imono Argo Indah Purwantini Intan Intan Iratutisisilia, Iratutisisilia Iskandar Ladamay, Iskandar Jenny Tandi Juwita, Dewi Ratna Kasih, Nirvane Zefanya Khusniyah, Farikhatul Kornelia Kidi Olarne Kristini, Wanda Kusumawati, Dina Ari Laviandhy, Debby Arthi Lianty, Nozylianty Liberti Natalia Hia Lukman Hakim Lukman Hakim Maharani, Devi Mahmudah, Amirotul M.H Margolang, Khairul Fadhli Margono, Supardjan A. Marlyn Dian Laksitorini Moh Salimi Muamaroh, Dzun Nur Nafi’ah Muassomah Muassomah Muhammad Faqih Muhammad Thamrin Nadia Leony L.W Neilcy Tjahja Mooniarsih Ningrum, Anita Dwi Juwita Norsandy, Dedi Nugroho, Agung Endro Nurhusna, Siti Deviana Rahma Nurul Qomariah Pakpahan, Aston Poetra, Bilal Ambara Herlando Pradana, Muhammad Yudha Pramudia, Yogha Primasari, Firdhani Satia Pudjono, Pudjono Purwatiningsih Purwatiningsih Putri, Hasna Tantowi Qotrunnada, Maulida Hasbiya Qowlits Tsabita, Qonita Qorrie Aini Raihan, Muhammad Retno Murwanti Riptasari, Rhatna Dewi Rosmawiah Rosmawiah Roziki, Khafid Safitri, Saktya Dea Samrotul Fikriyah Sandiki, Frisilia Dewanti Sandy, Trio May Sesanti, Nyamik Rahayu Sibarani, Edi Budi Harjono Silvia Arianti Simanjuntak, Marthin Yohannes Simanjuntak, Martin Yohannes Siti Nurrohmah SRI RAHAYU Sudibyo Martono Sukmarini, Zhafira Sumiatie Sumiatie Syahrir Akil Tampubolon, Laswandi Tangkasiang, Yos Andy Tri Lestari Triwayuningtyas, Dyah Ugang, Yandi Wahyono, Djoko Wahyono, Djoko Wibowo, Friza Rahmawanto Wulandari, Diana Yaakob, Mohd. Faiz Mohd Yani, Asnita Yanti, Elyta Vivi Yuliana, Palupi Dwi Yulianti Yulianti Yustha, Yulia Zahra, Husna wati Zullies Ikawati