• Title/Summary/Keyword: Cmax

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Bioequivqlence of Gabarep Tablet to Neurotin Tablet (Gabapentin 800 mg) (가바렙정 (가바펜틴 800 mg)의 생물학적 동등성 평가)

  • Seo, Young-Hwan;Jeong, Ju-Cheol;Lee, Jae-Young;Li, Zheng-Yi;Yoon, Hyoung-Jong;Sohn, Uy-Dong;Bang, Joon-Seok;Kim, Ho-Hyun;Jeong, Ji-Hoon
    • Journal of Pharmaceutical Investigation
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    • v.38 no.4
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    • pp.261-267
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    • 2008
  • The aim of the present study was to evaluate the bioequivalence of two gabapentin preparations. We used Neurontin tablet 800 mg (Pfizer Korea Inc.) as a reference drug for bioequivalence of Gabalep tablet 800 mg (Chong Kun Dang Pharmaceutical Co., Korea), and performed this whole study according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty five healthy male volunteers were administered with each drug in a randomized $2{\times}2$ cross-over study with one week washout interval. After drug administration, blood was taken at predetermined time intervals ($0{\sim}24$ hours) and the concentrations of gabapentin in serum were determined using an high performance liquid chromatography-tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction mornitoring (MRM). The analytical method was validated in specificity, accuracy, precision and linearity. The phar-macokinetic parameters such as AUCt and Cmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUCt and Cmax. $Mean{\pm}SD$. of AUCt and Cmax value for reference drug and test drug were $29.94{\pm}9.23\;({\mu}g/mL{\cdot}hr)$ and $3.12{\pm}1.11\;({\mu}g/mL{\cdot}hr)$, and $31.48{\pm}9.77\;({\mu}g/mL{\cdot}hr)$ and $3.15{\pm}1.03\;({\mu}g/mL)$, respectively. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) for AUCt and Cmax, respectively. These results indicate that Gabalep tablet 800 mg is bioequivalent to Neurontin tablet 800 mg.

Effects of temperature on pharmacokinetics of oxolinic acid in black rockfish, Sebastes schlegeli following oral administration (조피볼락, Sebastes schlegeli에 경구투여된 oxolinic acid의 약물동태에 미치는 수온의 영향)

  • Jung, Sung-Hee;Kim, Jin-Woo;Seo, Jung-Soo;Jee, Bo-Young;Park, Myoung-Ae
    • Journal of fish pathology
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    • v.23 no.2
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    • pp.221-227
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    • 2010
  • Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of oxolinic acid (OA) were studied after oral administration to cultured black rockfish, Sebastes schlegeli. Serum concentrations of OA were determined using HPLC-UV detector after a single dosage of 60 mg/kg body weight (average about 500 g). The peak serum concentrations of OA at $23{\pm}1.5^{\circ}C$ and $13{\pm}1.5^{\circ}C$ were $0.60{\mu}/ml$ at 30 h and $2.22{\mu}g/ml$ at 10 h post-dose, respectively. Better absorption of OA was noted at $13{\pm}1.5^{\circ}C$ compared to $23{\pm}1.5^{\circ}C$. The elimination of OA from serum was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. Both absorption and elimination of OA were affected significantly by temperature. The kinetic profile of absorption, distribution and elimination of OA in serum was analyzed by fitting to a two compartment model, with WinNonlin program. The AUC, Tmax and Cmax at $23{\pm}1.5^{\circ}C$ were $42.16{\mu}g{\cdot}h/m\ell$, 26.13 h and $0.43{\mu}g/ml$, respectively. The AUC, Tmax and Cmax at $13{\pm}1.5^{\circ}C$ were $131.98{\mu}g{\cdot}h/ml$, 8.81 h and $2.04{\mu}g/ml$, respectively.

Bioequivalency and Pharmacokinetics of Two Clarithromycin Tablets (Clarithromycin 정제의 생물학적 동등성 및 약물동태)

  • Kang, Won Ku;Park, Sun Young;Park, Yong Soon;Woo, Jong Su;Choi, Kyung Eob;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.49-54
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    • 1999
  • This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of $Klaricid^{(R)}$ The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters ($AUC_{0-l2hr}$, Cmax, Tmax, $AUC_{inf}$, Ka, Kel, $t_{1/2}$, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor $l/y^2$ was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters ($AUC_{0-l2hr},\;AUC_{inf}$, Cmax and Tmax) of Hanmi clarithromycin were $10.7\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;12.7\pm0.7\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.7\pm0.1\;{\mu}g/ml\;and\;2.0\pm0.2\;hr$, respectively, and those of $Klaricid^{(R)}\;were\;9.8\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;11.7\pm0.6\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.6\pm0.1\;{\mu}g/ml\;and\;2.1\pm0.1\;hr$, respectively. The differences in mean values of $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax between two products were $9.88\%,\;8.94%\;and\;6.59\%$, respectively. The least significant differences at $\alpha=0.05$ for $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax were $16.08\%,\;17.81\%\;and\;18.94\%$, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of $Klaricid^{(R)}$ at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of $Klaricid^{(R)}$. The Ka, Kel, $t_{1/2}$, Vd/F and Cl/F of the Hanmi clarithromycin were $2.69\pm0.53\;hr^{-1},\;0.18\pm0.01 hr^{-1},\;3.9\;hr,\;248.8\pm11.4\;L\;and\;43.7\pm2.6\;L/hr$, respectively, and those of $Klaricid^{(R)} were 2.19\pm0.51\;hr^{-1},\;0.18\pm0.02\;hr^{-1},\;3.7\;hr,\;266.7\pm22.4\;L\;and\;45.3\pm2.8L/hr$, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.

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Comparison of Parametric and Bootstrap Method in Bioequivalence Test

  • Ahn, Byung-Jin;Yim, Dong-Seok
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.367-371
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    • 2009
  • The estimation of 90% parametric confidence intervals (CIs) of mean AUC and Cmax ratios in bioequivalence (BE) tests are based upon the assumption that formulation effects in log-transformed data are normally distributed. To compare the parametric CIs with those obtained from nonparametric methods we performed repeated estimation of bootstrap-resampled datasets. The AUC and Cmax values from 3 archived datasets were used. BE tests on 1,000 resampled data sets from each archived dataset were performed using SAS (Enterprise Guide Ver.3). Bootstrap nonparametric 90% CIs of formulation effects were then compared with the parametric 90% CIs of the original datasets. The 90% CIs of formulation effects estimated from the 3 archived datasets were slightly different from nonparametric 90% CIs obtained from BE tests on resampled datasets. Histograms and density curves of formulation effects obtained from resampled datasets were similar to those of normal distribution. However, in 2 of 3 resampled log (AUC) datasets, the estimates of formulation effects did not follow the Gaussian distribution. Bias-corrected and accelerated (BCa) CIs, one of the nonparametric CIs of formulation effects, shifted outside the parametric 90% CIs of the archived datasets in these 2 non-normally distributed resampled log (AUC) datasets. Currently, the 80~125% rule based upon the parametric 90% CIs is widely accepted under the assumption of normally distributed formulation effects in log-transformed data. However, nonparametric CIs may be a better choice when data do not follow this assumption.

Studies on the Bioequivalence Test of Isoniazid Tablets (시판 이소니아짓 정제의 생물학적 동등성시험에 관한 연구)

  • Choi, Jun-Shik;An, Seon-Yeob
    • YAKHAK HOEJI
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    • v.33 no.4
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    • pp.229-236
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    • 1989
  • Even though two different preparations are chemically equivalent, the variance of bioavailability differenciates the clinical effect of preparations, so that the preparations need to be evaluated by comparing bioavailability in vivo as well as chemical equivalence. In this study, bioequivalence tests of commercially available isoniazid tablets A, B, C and D (standard) were performed to give some guidelines to bioequivalence test. The bioavailability parameters obtained by drug administeration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance for a cross over design. Cross over design was employed with 8 healthy volunteers. The results were within 20% difference of mean value in the AUC, Cmax, Tmax and amount of urinary excretion (Au) between standard and isoniazid tablets. The results of ANOVA showed no significant differences for 'group or sequence', but almost not for 'between subjects'. The tablet. A, B and D were within 20 min, but tablet C was within 50 min. Tablet A was biologically equivalent in the Au. tablet B biologically equivalent in the Au and AUC. Tablet C was biologically equivalent in the Au. The relationship between the dissolution rate and Au was significant.

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Pharmacokinetic Profiles of Isoniazid and Rifampicin in Korean Tuberculosis Patients (한국인 결핵환자에서 Isoniazid와 Rifampicin의 약동학)

  • Ahn, Seok-Jin;Park, Sang-Joon;Kang, Kyeong-Woo;Suh, Gee-Young;Chung, Man-Pyo;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Cha, Hee-Soo;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.442-450
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    • 1999
  • Background : Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. Methods : Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB 800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonrenal clearance(CLnr), and renal clearance(CLr) were calculated. Results : 1) Pharmacokinetic parameters of INH were as follows: Cmax; $7.63{\pm}3.20{\mu}g/ml$, Tmax; $0.73{\pm}0.22hr$, half-life; $2.12{\pm}0.84hrs$, Ke; $0.83{\pm}0.15hrs^{-1}$, CLtot; $17.54{\pm}8.89L/hr$, CLnr; $14.74{\pm}8.35L/hr$, CLr; $2.79{\pm}1.31L/hr$. 2) Pharmacokinetic parameters of RFP were as follows: Cmax; $8.93{\pm}3.98{\mu}g/ml$, Tmax; $1.76{\pm}1.13hrs$, half-life; $2.27{\pm}0.54hrs$, Ke; $0.32{\pm}0.08hrs^{-1}$, CLtot; $14.63{\pm}6.60L/hr$, CLr; $1.04{\pm}0.55L/hr$, CLnr; $13.59{\pm}6.21L/hr$. 3) While the correlation between body weight and Cmax of INH was not statistically significant (r=-0.514, p value>0.05), Cmax of RFP was significantly affected by body weight of the patients(r=-0.662, p value<0.01). Conclusion : In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.

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Pharmacokinetic Study of Isoniazid and Rifampicin in Healthy Korean Volunteers (정상 한국인에서의 Isoniazid와 Rifampicin 약동학 연구)

  • Chung, Man-Pyo;Kim, Ho-Cheol;Suh, Gee-Young;Park, Jeong-Woong;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Han, Yong-Chol;Park, Hyo-Jung;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.479-492
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    • 1997
  • Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

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Rainfall Intensity Estimation Using Geostationary Satellite Data Based on Machine Learning: A Case Study in the Korean Peninsula in Summer (정지 궤도 기상 위성을 이용한 기계 학습 기반 강우 강도 추정: 한반도 여름철을 대상으로)

  • Shin, Yeji;Han, Daehyeon;Im, Jungho
    • Korean Journal of Remote Sensing
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    • v.37 no.5_3
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    • pp.1405-1423
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    • 2021
  • Precipitation is one of the main factors that affect water and energy cycles, and its estimation plays a very important role in securing water resources and timely responding to water disasters. Satellite-based quantitative precipitation estimation (QPE) has the advantage of covering large areas at high spatiotemporal resolution. In this study, machine learning-based rainfall intensity models were developed using Himawari-8 Advanced Himawari Imager (AHI) water vapor channel (6.7 ㎛), infrared channel (10.8 ㎛), and weather radar Column Max (CMAX) composite data based on random forest (RF). The target variables were weather radar reflectivity (dBZ) and rainfall intensity (mm/hr) converted by the Z-R relationship. The results showed that the model which learned CMAX reflectivity produced the Critical Success Index (CSI) of 0.34 and the Mean-Absolute-Error (MAE) of 4.82 mm/hr. When compared to the GeoKompsat-2 and Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN)-Cloud Classification System (CCS) rainfall intensity products, the accuracies improved by 21.73% and 10.81% for CSI, and 31.33% and 23.49% for MAE, respectively. The spatial distribution of the estimated rainfall intensity was much more similar to the radar data than the existing products.

Omeprazole 체내 동태의 약물유전학적 특성에 관한 연구

  • 신상구;장인진;신재국;손동렬
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.334-334
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    • 1994
  • Omeprazole의 약동학적 Parameter는 tmax를 제외하고 두 군간에 유의한 (p<0.001) 차이론 보였다 : AUC의 평균치는 5-mephenytoin hydroxylation poor metabol izer에서 extensive metabol izer에 비해 약 6-7배 컸다. Omeprazole sulfone의 parameter는 omeprazole에서 관찰된 두 군간의 차이와 유사하였다. 그러나 5-hydroxyomeprazole의 경우에는 Cmax, AUC 등이 extensive metabolizer에서 더컸다. Omeprazole의 청소율은 S-mephenytoin hydroxylation 대사능(MR)과 유의한 상잔관계(rs=0.79, p<0.01)를 보였으며, omeprazole과 그 대사물(5-hydroxyomeprazole 및 omeprazole sulfone)의 반감기 또한 S-mephenytoin hydroxylation 대사능과 유의한 상관성을 보였다.

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Effects of Various Formulations on Bioavailability of Acetaminophen Soft Gelatin Capsules in Rabbits (토끼에서 아세트아미노펜 연집캅셀제의 생체이용율에 미치는 제제처방들의 영향)

  • Park, Gee-Bae;Lee, Yong-Suk;Choi, Myung-Ho;Lee, Do-Ik;Lee, Kwang-Pyo
    • YAKHAK HOEJI
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    • v.36 no.6
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    • pp.598-603
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    • 1992
  • The purpose of this study was to assess the effect of three formulations; product A (polyethylene glycol was used as a main dispersing agent), product B (wax mixture was used as a main dispersing agent) and product C(silicon dioxide was used as a main dispersing agent) on bioavailability of acetaminophen soft gelatin capsules(softgels) and to develop an effective acetaminophen softgel which exhibits an excellent bioavailability. Acetaminophen softgels of various formulations were prepared as 4 minim round type by rotary die method. Four softgels of the three formulation (A, B, C), each of which contained 50 mg acetaminophen, were administered orally to 12 normal healthy rabbits using a three-way cross over design. Plasma acetaminophen concentrations were measured by HPLC. The results obtained in this study were as follows: 1. The Tmax rank order of acetaminophen softgel was C$(63.75{\pm}10.62\;min)$>A$(36.25{\pm}5.37\;min)$>B$(35{\pm}6.74\;min)$. 2. The decreasing Cmax order of softgel product was A$(93.51{\pm}0.55\;{\mu}g/ml)$>B$(3.16{\pm}0.37\;{\mu}g/ml)$>C$(2.6{\pm}0.55\;{\mu}g/ml)$. 3. The $[AUC]^{\infty}_0$ rank order for three acetaminophen softgel formulations was A $(14.89{\pm}1.56\;{\mu}g/ml{\cdot}min)$ >B$(14.39{\pm}1.43\;{\mu}g/ml{\cdot}min)$>C$(11.45{\pm}1.49\;{\mu}g/ml{\cdot}min)$. 4. Pharmacokinetic parameters such as Tmax, Cmax and $[AUC]^{\infty}_0$ of product A and B did not differ significantly(p>0.05). On the other hand, those of product C were significantly different(p>0.05).

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