Doses Of HCl Research Articles

Bendamustine pharmacokinetic profile and exposure–response relationships in patients with indolent non-Hodgkin’s lymphoma

The pharmacokinetic profiles of bendamustine and active metabolites were defined in patients with rituximab-refractory, relapsed indolent B-cell non-Hodgkin's lymphoma, and supported understanding of exposure-response relationships for efficacy and safety. Bendamustine was administered as a 60-min 120 mg/m(2) intravenous infusion on days 1 and 2 of six 21-day cycles. Pharmacokinetic models were developed, with covariate assessment. Correlations between bendamustine exposure and responder status or occurrence of neutropenia, thrombocytopenia, fatigue, nausea, and vomiting were examined. Following a single dose of bendamustine HCl, concentrations declined in a triphasic manner, with rapid distribution, intermediate, and slow terminal phases. The intermediate t (1/2) (40 min) was considered the pharmacologically relevant (beta elimination) t (1/2) since the initial phases accounted for 99% of the AUC. Age, sex, mild/moderate renal, or mild liver impairment did not alter pharmacokinetics. Metabolite concentrations were low relative to parent. No correlation was observed between exposure and safety or efficacy measures because of the limited range of exposures after 120 mg/m(2) administration, except bendamustine C (max) was a significant (P value = 0.013) predictor of the probability of nausea in patients, most of whom were pretreated with antiemetics. The BSA-based dosing regimen for bendamustine achieved the targeted exposure and was associated with a high incidence of therapeutic response. Given the short t (1/2) and low concentrations of bendamustine observed by 12 h after dosing, the single-dose profile for bendamustine described by these analyses is expected to be representative of the multiple-dose profile. The occurrence of nausea was significantly related to bendamustine exposure, with the probability of nausea increasing as bendamustine C (max) increases.

Quantitative Analyses and Transcriptomic Profiling of Circulating Messenger Rnas As Biomarkers of Rat Liver Injury

Serum aminotransferases have been the clinical standard for evaluating liver injury for the past 50-60 years. These tissue enzymes lack specificity, also tracking injury to other tissues. New technologies assessing tissue-specific messenger RNA (mRNA) release into blood should provide greater specificity and permit indirect assessment of gene expression status of injured tissue. To evaluate the potential of circulating mRNAs as biomarkers of liver injury, rats were treated either with hepatotoxic doses of D-(+)-galactosamine (DGAL) or acetaminophen (APAP) or a myotoxic dose of bupivacaine HCl (BPVC). Plasma, serum, and liver samples were obtained from each rat. Serum alanine aminotransferase and aspartate aminotransferase were increased by all three compounds, whereas circulating liver-specific mRNAs were only increased by the hepatotoxicants. With APAP, liver-specific mRNAs were significantly increased in plasma at doses that had no effect on serum aminotransferases or liver histopathology. Characterization of the circulating mRNAs by sucrose density gradient centrifugation revealed that the liver-specific mRNAs were associated with both necrotic debris and microvesicles. DGAL treatment also induced a shift in the size of plasma microvesicles, consistent with active release of microvesicles following liver injury. Finally, gene expression microarray analysis of the plasma following DGAL and APAP treatment revealed chemical-specific profiles. The comparative analysis of circulating liver mRNAs with traditional serum transaminases and histopathology indicated that the circulating liver mRNAs were more specific and more sensitive biomarkers of liver injury. Further, the possibility of identifying chemical-specific transcriptional profiles from circulating mRNAs could open a range of possibilities for identifying the etiology of drug/chemical-induced liver injury.

Preparation, Optimisation and Characterisation of Lyophilised Rapid Disintegrating Tablets Based on Gelatin and Saccharide

Despite recent success, rapidly disintegrating lyophilized tablets still face problems of low mechanical strength and higher disintegration times resulting in poor patient compliance. The aim of the current work was to carry out a systematic study to understand the factors controlling mechanical properties of these formulations. The work investigated the influence of two bloom strengths of gelatin: low (60 bloom) and high (225 bloom) at different stock solution concentrations (2, 5, 7.5, and 10 %w/w). This was followed by investigation of addition of five saccharides (xylitol, glucose, trehalose, maltotriose and mannitol) at varied concentration range (10-80 %w/w) to decipher their influence on disintegration time, mechanical and thermal properties of the formulation. The results indicated that the disintegration time of the tablets dramatically decreased by decreasing the concentration and bloom strength of gelatin in the stock solution. However the mechanical properties of the tablets were mainly influenced by the concentration of gelatin rather than the bloom strength. The addition of saccharides resulted in enhancement of tablet properties and was concentration dependent. All the saccharides improved the fractubility of the tablets significantly at high concentration (equal or higher than 40% w/w). However, only high concentration (equal or higher than 40% w/w) of trehalose, maltotriose and mannitol significantly enhanced the hardness. Additionally, mannitol crytallised during freeze drying and consequently produced elegant tablets, whilst the other saccarides exhibited lyoprotectant activity as they were able to retain amorphous status. Based on the above findings, an optimized formulation was also successfully developed and characterized to deliver 100 microg dose of Clonidine HCl.

Antinociceptive and gastro-protective effect of the ethanolic extract of the flowering top of Anthocephalus Cadamba Roxb

The effect of alcoholic extract of Anthocephalus (A.) Cadamba Roxb. was evaluated in experimental models of pain and ulcer. Hot tail flick test, hot plate test and acetic acid induced writhing test were employed for evaluating the peripheral as well as central analgesic mechanism exerted by the extracts. Gastroprotective activity was examined by HCl and ethanol induced gastric damage test. Test group received crude extract 500 mg/kg showed maximum time needed for the response against thermal stimuli (6.26 <TEX>${\pm}$</TEX> 0.439 s) which is comparable to diclofenac sodium (6.56 <TEX>${\pm}$</TEX> 0.381 s) in hot tail flick method. These experimental results also followed the experimental results of hot plate test where crude extract 500 mg/kg showed maximum time needed for the response against thermal stimuli (4.74 <TEX>${\pm}$</TEX> 0.234 s) which is comparable to diclofenac sodium (5.58 <TEX>${\pm}$</TEX> 0.585 s). The crude extract at 500 and 250 mg/kg showed significant reduction in acetic acid induced writhing in mice with a maximum effect of 68.026% reduction at 500 mg/kg dose which is comparable to standard diclofenac sodium (79.93%). In gastroprotective study the extract of A. Cadamba (250 and 500 mg/kg) significantly inhibited ulceration induced by both HCl and ethanol dose dependently. Results of the study suggest that the extract possesses both analgesic and gastroprotective activity on mice.

A multicenter, open-label, exploratory dose-ranging trial of intranasal hydromorphone for managing acute pain from traumatic injury

Abstract We conducted a prospective multicenter, open-label, escalating dose-range trial to compare, across patients, single intranasal doses (2, 4, 6, 8, and 10 mg) of hydromorphone HCl in the treatment of acute trauma pain The main outcome measure of pain-intensity reduction was derived from serial Numerical Pain-Rating Scores and calculated as the summed pain-intensity difference over 3 hours (SPID 3). Nasal examinations, vital signs, and adverse events were reported as safety outcomes. The mean decrease in pain intensity from baseline to 30 minutes was 39 to 44% for the 4-, 6-, 8- and 10-mg doses (n = 19, 33, 28, and 19 per group) and only 24% reduction for the 2-mg dose (n = 14). SPID 3 for the 2-mg dose was 40 to 50% below all other doses. There were no clinically meaningful changes in vital signs or nasal examinations. Adverse events (nausea, vomiting, pruritis, oxygen desaturation, bad taste, dizziness) were of mild to moderate intensity, increased with dose, and expected, based on route of administration and opioid pharmacology. Intranasal hydromorphone provides a component of rapid pain relief in the care of emergency department patients suffering from acute trauma pain. Perspective This article presents a pilot dose-ranging study of intranasally administered hydromorphone, administered in the emergency department to patients suffering from acute trauma pain. This study demonstrates research success in this setting and noninjection-based delivery and certain doses of intranasal hydromorphone may be effective in treating acute trauma pain.

Intravenous tramadol: effects, nociceptive properties, and pharmacokinetics in horses

ObjectiveTo determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse. Study designTwo-phase blinded, randomized, prospective crossover trial. AnimalsSeven horses (median age 22.5 years and mean weight 565 kg). MethodsHorses were treated every 20 minutes with incremental doses of tramadol HCl (0.1–1.6 mg kg−1) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL and STRL) to a thermal stimulus were determined 5 and 30 minutes, and 1, 2, 4 and 6 hours after bolus IV tramadol (2.0 mg kg−1) or vehicle. Blood samples were taken to determine pharmacokinetics. ResultsCompared to saline, tramadol caused no change in heart rate, step frequency or sweating score. Respiratory rate, head height, and head nodding and trembling scores were transiently but significantly increased and borborygmus score was decreased by high doses of tramadol. Following cumulative IV administration of 3.1 mg kg−1 and bolus IV administration of 2 mg kg−1, the elimination half-life of tramadol was 1.91 ± 0.33 and 2.1 ± 0.9 hours, respectively. Baseline HWRL and STRL were 4.16 ± 1.0 and 3.06 ± 0.99 seconds, respectively, and were not significantly prolonged by tramadol. Conclusion and clinical relevanceIV tramadol at cumulative doses of up to 3.1 mg kg−1 produced minimal transient side effects but 2.0 mg kg−1 did not provide analgesia, as determined by response to a thermal nociceptive stimulus.

A Multicenter, Open-Label, Exploratory Dose-Ranging Trial of Intranasal Hydromorphone for Managing Acute Pain from Traumatic Injury

We conducted a prospective multicenter, open-label, escalating dose-range trial to compare, across patients, single intranasal doses (2, 4, 6, 8, and 10 mg) of hydromorphone HCl in the treatment of acute trauma pain The main outcome measure of pain-intensity reduction was derived from serial Numerical Pain-Rating Scores and calculated as the summed pain-intensity difference over 3 hours (SPID 3). Nasal examinations, vital signs, and adverse events were reported as safety outcomes. The mean decrease in pain intensity from baseline to 30 minutes was 39 to 44% for the 4-, 6-, 8- and 10-mg doses (n = 19, 33, 28, and 19 per group) and only 24% reduction for the 2-mg dose (n = 14). SPID 3 for the 2-mg dose was 40 to 50% below all other doses. There were no clinically meaningful changes in vital signs or nasal examinations. Adverse events (nausea, vomiting, pruritus, oxygen desaturation, bad taste, dizziness) were of mild to moderate intensity, increased with dose, and expected, based on route of administration and opioid pharmacology. Intranasal hydromorphone provides a component of rapid pain relief in the care of emergency department patients suffering from acute trauma pain. This article presents a pilot dose-ranging study of intranasally administered hydromorphone, administered in the emergency department to patients suffering from acute trauma pain. This study demonstrates research success in this setting and noninjection-based delivery and certain doses of intranasal hydromorphone may be effective in treating acute trauma pain.

Effects of ractopamine HCl dose and treatment period on pig performance in a commercial finishing facility (2009)

Effects of ractopamine HCl dose and treatment period on pig performance in a commercial finishing facility (2009)

Single Dose Analgesic Efficacy of Tapentadol in Postsurgical Dental Pain: The Results of a Randomized, Double-Blind, Placebo-Controlled Study

Tapentadol is a novel, centrally acting analgesic with two modes of action, combining mu-opioid agonism and norepinephrine reuptake inhibition in a single molecule. We compared the efficacy and tolerability of tapentadol and a standard dose of morphine with placebo in a model of moderate-to-severe postoperative dental pain. Patients undergoing mandibular third molar extraction and experiencing moderate-to-severe pain postsurgery were randomized to receive single, oral doses of tapentadol HCl (25, 50, 75, 100, or 200 mg), morphine sulfate (60 mg), ibuprofen (400 mg; used to establish model sensitivity), or placebo. Mean total pain relief over 8 h (TOTPAR-8) was the primary end point. Secondary end points included mean total pain relief over 4 h (TOTPAR-4) and onset of analgesia. Pairwise comparisons of study drug to placebo were assessed using the Fisher least significant difference test. Adverse events were recorded. Four hundred patients were randomized to treatment and completed the study. Compared with placebo, mean TOTPAR-8 was significantly greater for tapentadol HCl 50 mg (P = 0.041), 75 mg (P = 0.001), 100 mg (P < 0.001), and 200 mg (P < 0.001); morphine sulfate 60 mg (P < 0.001); and ibuprofen 400 mg (P < 0.001) in a nonparametric analysis of the primary end point. The significantly higher TOTPAR-8 score for ibuprofen compared with placebo established the sensitivity of the model. Mean TOTPAR-4 was higher and onset of action appeared more rapid for tapentadol HCl 200 mg than morphine sulfate 60 mg. Pain relief scores with morphine sulfate 60 mg were between those of tapentadol HCl 100 and 200 mg. The incidence of nausea and vomiting appeared to be lower with all doses of tapentadol HCl compared with morphine sulfate 60 mg, but was not statistically significant. Single oral doses of tapentadol 75 mg or higher effectively reduced moderate-to-severe postoperative dental pain in a dose-related fashion and were well-tolerated relative to morphine. These data suggest that tapentadol is a highly effective, centrally acting analgesic with a favorable side effect profile and rapid onset of action.

Palonosetron—A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study

Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.

Alcohol significantly lowers the seizure threshold in mice when co-administered with bupropion hydrochloride

BackgroundBupropion HCl is a widely used antidepressant that is known to cause seizures in a dose-dependent manner. Many patients taking antidepressants will consume alcohol, even when advised not to. Previous studies have not shown any interactions between bupropion HCl and alcohol. However, there have been no previous studies examining possible changes in seizure threshold induced by a combination of alcohol and bupropion HCl.MethodsExperimentally naïve female Swiss albino mice (10 per group) received either single doses of bupropion HCl (ranging from 100 mg/kg to 120 mg/kg) or vehicle (0.9% NaCl) by intraperitoneal (IP) injection in a dose volume of 10 ml/kg, and single-dose ethanol alone (2.5 g/kg), or vehicle, 5 min prior to bupropion dosing. The presence or absence of seizures, the number of seizures, the onset, duration and the intensity of seizures were all recorded for 5 h following the administration of ethanol.ResultsThe results show that administration of IP bupropion HCl alone induced seizures in mice in a dose-dependent manner, with the 120 mg/kg dose having the largest effect. The percentage of convulsing mice were 0%, 20%, 30% and 60% in the 0 (vehicle), 100, 110, and 120 mg/kg dose groups, respectively. Pretreatment with ethanol produced a larger bupropion HCl-induced convulsive effect at all the doses (70% each at 100, 110 and 120 mg/kg) and a 10% effect in the ethanol + vehicle only group. The convulsive dose of bupropion HCl required to induce seizures in 50% of mice (CD50), was 116.72 mg/kg for bupropion HCl alone (CI: 107.95, 126.20) and 89.40 mg/kg for ethanol/bupropion HCl (CI: 64.92, 123.10).ConclusionThese results show that in mice alcohol lowers the seizure threshold for bupropion-induced seizures. Clinical implications are firstly that there may be an increased risk of seizures in patients consuming alcohol, and secondly that formulations that can release bupropion more readily in alcohol may present additional risks to patients.

Correction of metabolic acidosis after conversion from sevelamer hydrochloride to lanthanum carbonate.

Sir,We recently introduced lanthanum carbonate as an alter-native phosphate binder to sevelamer hydrochloride in pa-tients with elevated serum calcium. Lanthanum carbonatehas a higher affinity for phosphate than sevelamer HCl, sofewer lanthanum carbonate tablets are required to achievethe same phosphate control. To reduce the pill burden inpatients on high doses of sevelamer HCl, a policy of con-verting patients who were prescribed 8–12 sevelamer perday, and patients currently on 6 sevelamer per day but inneed of a dose increase, to 3 × 750 mg lanthanum car-bonate per day was established. Conversions were made atthe discretion of the doctor, so that well-controlled patientswere less likely to switch.In October 2007, 60 haemodialysis patients convertedaccording to the above criteria. Of these, 13 patients whodislikedorwereintolerantoflanthanumcarbonaterevertedto sevelamer HCl within 3 months. Forty-seven patients(68% male, median age 47 years, range 21–79) continuedto take lanthanum carbonate.Several studies have suggested that sevelamer HCl con-tributes to metabolic acidosis [1,2], while lanthanum car-bonate would be expected to have an antacid effect. Acomparison of the median of three routine (monthly) pre-dialysis serum bicarbonate and phosphate measurementsimmediately before and after conversion for each patientshowed an increase in serum bicarbonate from a meanof 20.3 ± 2.3 to 22.2 ± 2.4 mmol/l (

Pharmacokinetics and Absolute Bioavailability of Selegiline Following Treatment of Healthy Subjects With the Selegiline Transdermal System (6 mg/24 h): A Comparison With Oral Selegiline Capsules

The selegiline transdermal system is a monoamine oxidase inhibitor that was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. The current study was conducted during the selegiline transdermal system development program to characterize the single-dose pharmacokinetics and absolute bioavailability of selegiline administered by the 6-mg/24-h selegiline transdermal system in healthy volunteers. Selegiline transdermal system results were compared with those obtained after a single 10-mg oral dose of selegiline HCl. The selegiline pharmacokinetics differed greatly between the 2 routes of administration. Transdermal selegiline administration reduced metabolism and produced a high, sustained plasma selegiline concentration over the dosing period, with an absolute bioavailability of 73%. By contrast, oral dosing produced a sharp plasma selegiline peak that occurred within 1 hour and declined rapidly, with an absolute bioavailability of 4%. The data provide the basis for therapeutic advantages of the selegiline transdermal system in administering antidepressant doses of selegiline.

Safety, Tolerability, QTc Evaluation, and Pharmacokinetics of Single and Multiple Doses of Enzastaurin HCl (LY317615), a Protein Kinase C‐β Inhibitor, in Healthy Subjects

The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and its metabolites ranged from approximately 12 to 40 hours. The longer half-life of the major circulating and pharmacologically active metabolite allowed once-a-day dosing and predicted that steady state would be achieved within 2 weeks of daily oral dosing in all subjects. In the multiple-dose study, daily doses (25-400 mg) were examined, with 24 subjects receiving at least 1 dose. The most common adverse events related to enzastaurin were headache, sleepiness, diarrhea, and nausea. No clinically significant changes in QTc intervals were observed. Overall, enzastaurin was well tolerated in healthy subjects, and the planned maximum dose was achieved in both studies.

Transient acid exposure increases sevelamer HCl phosphate binding

The patient-to-patient variability in the dosing of sevelamer HCl for phosphate control led us to test whether the binder's transient exposure to acidic environments (such as the stomach) might alter the compound so as to change its subsequent binding capacity in the more alkaline small intestine. We hypothesized that an acid milieu could either increase the reactive sites (protonated amine groups) or make the polymer more hydrophilic (hydration and swelling allowing more phosphate to reach those sites). Eight hundred milligrams of Renagel tablets were exposed to pHs 1, 2.3, and 7 (n = 7 each acidity level) for 1 h. NaCl was added to keep ionic strength the same. Measured by atomic emission phosphate uptake after 3 h at pH 7 was, respectively, 3.13 +/- 0.21, 2.72 +/- 0.35, and 1.85 +/- 0.46 mequiv./g (p = 0.0006, pH 1 vs. pH 7). Semi-automated computerized image analysis was then performed to measure swelling of the particles. We constructed a glass continuous-flow cell that allowed stationary particles and real-time photography. Using digitized optical measurements there was no difference (p > 0.8) between the swelling after 1 h of pH 1 or 7 solutions (60.2 +/- 14.8% vs. 59.5 +/- 9.8% increase in diameter). Our findings support the importance of transient acid exposure in enhancing phosphate binding, due to increased protonated sites rather than by more swelling. Patients with acquired or pharmacologic achlorhydria would not benefit from this unexpected in vivo reaction. Possibly manufacturing sevelamer with a higher degree of protonation or administering it with appropriately acidic vehicles or beverages remains to be investigated.

The Pharmacokinetics of Cinacalcet are Unaffected Following Consumption of High- and Low-Fat Meals

Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet is administered orally, and thus concomitant administration with food may affect its bioavailability. The objective of this study was to examine the effect of fat and caloric intake on cinacalcet exposure. This phase 1, randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral dose of cinacalcet HCl (Sensipar/Mimpara; Amgen Inc. Thousand Oaks, CA) (90 mg) on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low-caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to 72 hours postdose for pharmacokinetic (AUCinfinity, Cmax) and safety evaluations. Twenty-nine subjects completed all the 3 treatment conditions. The mean (90% confidence intervals) AUCinfinity following high- and low-fat meals was increased by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The difference in mean AUCinfinity between high- and low-fat meals was small [12 (9.9-26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2beta was similar between treatment conditions. Adverse events (AE) were observed at a similar frequency across the treatment conditions [high fat (34%), low fat (23%), and fasting (31%)]; the type of AE did not differ among the treatment conditions. The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30 (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. However, the small differences observed in exposure following the ingestion of the different types of meals suggest that although food has a significant effect, the type of food does not. The observed effect supports the labeling statement that cinacalcet be taken with food, or shortly after a meal.

The effects of glucosamine hydrochloride on subchondral bone changes in an animal model of osteoarthritis

To quantify periarticular subchondral bone changes in a rabbit model of experimental osteoarthritis (OA), and to determine the effects of continuous administration of a clinically relevant dose of glucosamine HCl on subchondral bone changes in this model. Anterior cruciate ligament transection (ACLT) was performed on the left femorotibial joints of 16 rabbits to induce OA. Ten rabbits that did not undergo ACLT served as unoperated controls. Eight rabbits that underwent ACLT and 6 control rabbits were treated with 100 mg of glucosamine daily, and the others were given a placebo. The articular cartilage was evaluated macroscopically and graded at the time of necropsy, 8 weeks after ACLT. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry on the dissected distal femur and proximal tibia. Subchondral trabecular bone turnover, architecture, and connectivity, as well as subchondral plate thickness and mineralization were studied on the undecalcified tibia sections from each animal. Eight weeks after ACLT, most of the operated joints had various degrees of cartilage damage and fibrillation. Compared with the control group, the ACLT group had significantly increased subchondral bone turnover and lower BMD, bone volume, connectivity, and bone mineralization. The high bone turnover was significantly reduced in glucosamine-treated animals that underwent ACLT. In fact, there were no significant differences between the ACLT/glucosamine group and the control/glucosamine group in most of the bone parameters studied. This study shows that subchondral bone turnover, structure, and mineralization are significantly altered in the early stages of experimental OA, and that these changes are attenuated by glucosamine treatment.

Considerable interindividual variation in the pharmacokinetics of tolperisone HCl

The aim of this study was to determine the pharmacokinetic profiles of oral tolperisone hydrochloride in healthy volunteers. After the oral administration of tolperisone hydrochloride, the plasma concentrations of tolperisone were measured in 15 healthy male Korean volunteers. The tolperisone concentration was determined using high-performance liquid chromatography with a C18 reverse-phase column. Very large interindividual differences in the AUC and Cmax were detected after oral tolperisone HCl. The AUC0-infinity, varied from 125.9-1,241.3 ng/ml x h, and the Cmax varied from 64.2 and 784.9 ng/ml. The tmax of tolperisone was 0.90 +/- 0.31 h and the mean half-life was 1.00 +/- 0.28 h. These results suggest that the pharmacological effect of oral tolperisone HCl varies between individuals, and the oral tolperisone HCl dose might need to be individualized.

Design and evaluation of a floating ranitidine tablet as a drug delivery system for oral application

In recent years, scientific and technological advances have been made in the research and development of rate-controlled oral drug delivery systems by overcoming physiological obstacles, such as short gastric residence times (GRT), and unpredictable gastric emptying times. Several approaches are currently utilized in the prolongation of GRT, including floating drug delivery systems (FDDs). A drug delivery system for the water-soluble H 2 -receptor antagonist drug, ranitidine hydrochloride, was developed. The floating and controlled-release properties of tablets containing ranitidine HCl, hydroxypropylmethylcellulose (HPMC), and different additives were examined. The study shows that tablet composition and mechanical strength have the greatest influence on floating properties and drug release. Sodium bicarbonate was used as gas-generating agent which enhances tablet flotation. The time taken for tablets to emerge on the water surface (floating lag time), or buoyant time, and the time during which the tablets constantly float on the water surface (duration of floating) were evaluated in a dissolution vessel. The results indicated that buoyancy is strong enough for whole tablets to travel up to the surface and remain on the surface for as long as 24 h. In vitro dissolution was carried out in simulated gastric fluid (enzyme-free) at 37 ± 0.5°C as per USP 22. Drug release from the tablets was sufficiently sustained (12 h) compared to conventional tablets. Drug release best fit both the Higuchi and Peppas models. Moreover, the effect of tablet hardness and stirring rate on the release kinetics was examined. The floating tablets were compared with conventional tablets in fasted rabbits at 150 mg equivalent dose of ranitidine HCl. The pharmacokinetic parameters, maximum plasma concentration (C max ), the time to reach maximum plasma concentration (T max ), and the area under plasma concentration curve (AUC) for 0-12 h were calculated. The relative bioavailability of the floating tablets in relation to the conventional tablets was also calculated.

The 30 mg Dose of Fexofenadine HCl 6 mg/mL Suspension is Bioequivalent to the Marketed 30 mg Tablet in Healthy Adult Subjects under Fasted Conditions: a Randomized, Crossover, Open-label Study

The 30 mg Dose of Fexofenadine HCl 6 mg/mL Suspension is Bioequivalent to the Marketed 30 mg Tablet in Healthy Adult Subjects under Fasted Conditions: a Randomized, Crossover, Open-label Study