Articles
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
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DOI: 10.14499/indonesianjpharm27iss2pp99
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
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DOI: 10.14499/indonesianjpharm0iss0pp244-249
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
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DOI: 10.14499/indonesianjpharm0iss0pp163-168
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
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DOI: 10.14499/indonesianjpharm23iss3pp183-187
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, GenericÂ
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
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DOI: 10.14499/indonesianjpharm0iss0pp194-198
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
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DOI: 10.14499/indonesianjpharm28iss4pp205
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
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DOI: 10.14499/indonesianjpharm0iss0pp204-211
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
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DOI: 10.14499/indonesianjpharm0iss0pp169-176
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
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DOI: 10.14499/indonesianjpharm0iss0pp65-72
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
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DOI: 10.14499/indonesianjpharm0iss0pp117-123
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