Two different salts of diclofenac, diclofenac sodium and dielofenae potassium, in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study. Biochemical and physiological parameters were also measured in both normal and dehydrated states. Diclofenac levels in plasma were determined using a validated reversed phase HPLC method. Primary kinetic parameters i.e. AUC0-∞, Cmax, Tmax and other disposition kinetics were obtained with non-compartmental procedure. Biochemical parameters i.e. packed cell volume, plasma glucose and total lipid concentration in dehydrated rabbits increased significantly. Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits. In comparison, diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.

STUDY DESIGN: Randomized controlled trial. PURPOSE: The purpose of this study was to compare pregabalin and gabapentin for mean postoperative visual analog score (VAS) for pain in patients undergoing single-level lumbar microdiscectomy for intervertebral disc prolapse at a tertiary care hospital. OVERVIEW OF LITERATURE: Pregabalin has a superior pharmacokinetic profile and analgesic effect at lower doses than gabapentin; however, analgesic efficacy must be established during the perioperative period after lumbar spine surgery. METHODS: This randomized controlled trial was carried out at our institute from February to October 2011 on 78 patients, with 39 participants in each study group. Patients undergoing lumbar microdiscectomy were randomized to group A (gabapentin) or group B (pregabalin) and started on trial medicines one week before surgery. The VAS for pain was recorded at 24 hours and one week postoperatively. RESULTS: Both groups had similar baseline variables, with mean ages of 42 and 39 years in groups A and B, respectively, and a majority of male patients in each group. The mean VAS values for pain at 24 hours for gabapentin vs. pregabalin were comparable (1.97±0.84 vs. 1.6±0.87, respectively; p=0.087) as were the results at one week after surgery (0.27±0.45 vs. 0.3±0.46, respectively; p=0.79). None of the patients required additional analgesia postoperatively. After adjusting for age and sex, the VAS value for group B patients was 0.028 points lower than for group A patients, but this difference was not statistically significant (p=0.817, R²=0.018). CONCLUSIONS: Pregabalin is equivalent to gabapentin for the relief of postoperative pain at a lower dose in patients undergoing lumbar microdiscectomy. Therefore, other factors, such as dose, frequency, cost, pharmacokinetics, and side effects of these medicines, should be taken into account whenever it is prescribed.
Analgesia ; Humans ; Intervertebral Disc ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; Male ; Pain, Postoperative* ; Perioperative Period ; Pharmacokinetics ; Pregabalin* ; Prolapse ; Spine ; Tertiary Healthcare

STUDY DESIGN: This is a case series. PURPOSE: We wanted to identify variations in the practice patterns among neurosurgeons and orthopedic surgeons for the management of spinal disorders. OVERVIEW OF LITERATURE: Spinal disorders are common in the clinical practice of both neurosurgeons and orthopedic surgeons. It has been observed that despite the availability of various guidelines, there is lack of consensus among surgeons about the management of various disorders. METHODS: A questionnaire was distributed, either directly or via e-mail, to the both the neurosurgeons and orthopedic surgeons who worked at 5 tertiary care centers within a single region of Korea. The surgeons were working either in private practice or in academic institutions. The details of the questionnaire included demographic details and the specialty (orthopedic/neurosurgeon). The surgeons were classified according to the level of experience as up to 5 years, 6-10 years and > 10 years. Questions were asked about the approach to lumbar discectomy (fragmentectomy or aggressive disc removal), using steroids for treating discitis, the fusion preference for spondylolisthesis, the role of an orthosis after fusion, the preferred surgical approach for spinal stenosis, the operative approach for spinal trauma (early within 72 hours or late > 72 hours) and the role of surgery in complete spinal cord injury. The data was analyzed using SPSS ver 16. p-values < 0.05 were considered to be significant. RESULTS: Of the 30 surgeons who completed the questionnaire, 20 were neurosurgeons and 10 were orthopedic surgeons. Statistically significant differences were observed for the management of spinal stenosis, spondylolisthesis, using an orthosis after fusion, the type of lumbar discectomy and the value of surgical intervention after complete spinal cord injury. CONCLUSIONS: Our results suggest that there continues to exist a statistically significant lack of consensus among neurosurgeons and orthopedic spine surgeons when considering using an orthosis after fusion, the type of discectomy and the value of intervention after complete spinal injury.
Consensus ; Discitis ; Diskectomy ; Electronic Mail ; Korea ; Orthopedics ; Orthotic Devices ; Private Practice ; Spinal Cord ; Spinal Cord Injuries ; Spinal Injuries ; Spinal Stenosis ; Spine ; Spondylolisthesis ; Steroids ; Tertiary Care Centers ; Surveys and Questionnaires

Two different salts of diclofenac, diclofenac sodium and diclofenac potassium, in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study. Biochemical and physiological parameters were also measured in both normal and dehydrated states. Diclofenac levels in plasma were determined using a validated reversed phase HPLC method. Primary kinetic parameters i.e. AUC(0-infinity), Cmax, Tmax and other disposition kinetics were obtained with non-compartmental procedure. Biochemical parameters i.e. packed cell volume, plasma glucose and total lipid concentration in dehydrated rabbits increased significantly. Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits. In comparison, diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.
Administration, Oral ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Biological Availability ; Dehydration ; metabolism ; Diclofenac ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Rabbits ; Tablets

This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.

STUDY DESIGN: Retrospective case series. PURPOSE: The objective of our study was to determine the change in management brought about by magnetic resonance imaging (MRI) of the cervical spine in alert and awake patients with facet dislocation and spinal cord injury presenting within 4 hours after injury. OVERVIEW OF LITERATURE: Spinal cord injury is a common clinical entity. The role of MRI is well established in evaluating spinal trauma. However, the time at which MRI should be used is still controversial. METHODS: Retrospective data from 2002-2010 was evaluated. All of the alert and awake patients with spinal cord injury, based on clinical examination with facet dislocation diagnosed on lateral cervical spine X-rays, were included. A questionnaire was also conducted, the data of which consisted of demographic details including age and sex, the mechanism of injury, clinical examination, X-ray findings, MRI findings, whether or not surgery was performed and the time elapsed since injury. Data was analyzed using SPSS ver. 17.0. Continuous variables such as age were expressed in terms of mean +/- standard deviation. Categorical variables such as change in management, X-ray/MRI findings and neurological motor level were assessed in terms of percentage. RESULTS: Fifty patients participated in our study. All these patients had spinal cord injury with defined motor levels. The mean age was 35.5 +/- 8.95 years (range, 20 to 52 years). Fifty percent showed a motor level at C6 level. None of the patients required any change in management based on the MRI. CONCLUSIONS: MRI of the spine in awake patients within 4 hours after injury does not change the management of patients. However, we can hypothesize that such patients can proceed to traction without waiting for the MRI.
Dislocations ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Retrospective Studies ; Spinal Cord Injuries ; Spine ; Traction ; Surveys and Questionnaires

The aim of present study is to develop a pharmacokinetic model for microencapsulated metronidazole to predict drug absorption pattern in healthy human and validate this model internally. Metronidazole was microencapsulated into ethylcellulose shells followed by the conversion of these microcapsules into tablets. Dissolution study of tablets was conducted in 450 mL double distilled water, 0.1 mol L(-1) HCl and phosphate buffer (pH 6.8) maintained at (37+/-0.5) degrees C using USP apparatus II at 50, 100 and 150 r min(-1). Three metronidazole tablets (T1: fast release, T2: moderate release, T3: slow release and reference) were administered to twenty four healthy human volunteers and serial blood samples were collected for 12 hours followed by their analysis using RP-HPLC. Drug release data were analyzed by various model dependent and independent approaches. Drug absorbed (%) was determined by Wagner-Nelson method from plasma concentration profile. Internal predictability was checked from Cmax and AUC. Optimum dissolution profile was observed in double distilled water and 50 r min(-1). A good level A correlation was observed between drug dissolution and absorption profiles (correlation coefficient, R2 = 0.9009, 0.9426, 0.9015 and 0.932 for T1, T2, T3 and reference, respectively). Internal predictability was found less than 10%. Good correlation coefficients and low prediction errors elaborate the validity of this mathematical in-vitro in-vivo correlation model as a predictive tool for the determination of pharmacokinetics from dissolution data.
Chemistry, Pharmaceutical ; Drug Compounding ; Drug Design ; Humans ; Male ; Metronidazole ; administration & dosage ; pharmacokinetics ; Young Adult

This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.
Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Cross-Over Studies ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Humans ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; Microspheres ; Models, Chemical ; Sulfonamides ; administration & dosage ; pharmacokinetics

The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.

INTRODUCTIONMetabolic heterogeneity among obese individuals is thought to translate into variations in cardiovascular risk. Identifying obese people with an unfavourable metabolic profile may allow preventive strategies to be targeted at high-risk groups. This study aimed to identify clinical, biochemical and immunological differences between insulin-sensitive and insulin-resistant obese subgroups, to understand the population-specific pathophysiological basis of the adverse cardiovascular risk profile in the latter group.

METHODSCardiovascular risk indicators, including anthropometric parameters, blood pressure, acanthosis nigricans area, and related biochemical, endocrine and inflammatory markers, were determined in 255 healthy South Asian volunteers aged 18-45 years, with a 2:1 ratio of obese/overweight to normal-weight individuals. Lifetime atherosclerotic cardiovascular disease (ASCVD) risk was also calculated.

RESULTSBody mass index (BMI) and insulin sensitivity-based tertiles independently showed incremental trends in waist-hip ratio, skinfold thickness, acanthosis nigricans area, blood pressure, serum lipids, hepatic enzymes, adipokines, inflammatory markers and ten-year ASCVD risk. The anthropometric, biochemical and inflammatory parameters of obese insulin-sensitive and obese insulin-resistant groups differed significantly. Extreme group analysis after excluding the middle tertiles of both insulin resistance and BMI also showed significant difference in anthropometric indicators of cardiovascular risk and estimated lifetime ASCVD risk between the two obese subgroups.

CONCLUSIONObese insulin-sensitive individuals had a favourable metabolic profile compared to the obese insulin-resistant group. The most consistent discriminative factor between these phenotypic classes was anthropometric parameters, which underscores the importance of clinical parameters as cardiovascular risk indicators in obesity.