Comparison of pharmacokinetics and safety of fixed-dose combination of SKI306X and aceclofenac versus separate tablets in healthy subjects

JOINS (SKI306X) is an herbal anti-arthritic medicine that is widely used with aceclofenac for treating osteoarthritis in Korea. A fixed-dose combination (FDC) tablet containing SKI306X and aceclofenac was developed to improve patient compliance. This study aimed to compare the pharmacokinetics (PK) and safety of the FDC tablet with those of co-administered SKI306X and aceclofenac in healthy subjects. In this randomized, open-label, two-way crossover, single-dose study, the FDC tablet (SKI306X 300 mg/aceclofenac 100 mg) (test) was given or co-administration of 300 mg of SKI306X and 100 mg of aceclofenac (reference) was performed followed by a 7-day wash-out period. Blood samples were collected before and after drug administration to evaluate aceclofenac PK parameters, and safety was assessed throughout the study. A total of 54 healthy male subjects were enrolled in and completed the study. T(max) and t(1/2) of aceclofenac of the FDC tablet were similar to those of aceclofenac co-administered with SKI306X (T(max): test 2.96 h and reference 2.14 h; t(1/2): test 3.46 h and reference 4.04 h). The geometric mean ratios (90% confidence intervals) of C(max) and AUC(last) (T/R) were 0.85 (0.81 to 0.91) and 1.03 (1.01 to 1.06) respectively; these results were within the predefined range (0.8 to 1.25). There was only one drug-related adverse event (dizziness) occurred after administration of the FDC tablet; however, it was mild in severity and resolved without any complications. The FDC tablet was well tolerated and exhibited an absorption rate and extent comparable to those of SKI306X and aceclofenac administered simultaneously.

Effects of JOINS® on the pharmacokinetic profiles of aceclofenac in healthy Korean volunteers: an open-label, multiple-dose, one sequence, two-period study

JOINS, an herbal anti-arthritic drug, was developed for the treatment and pain relief of knee osteoarthritis. It was approved for use in Korea by the Ministry of Food and Drug Safety in 2001. The aim of this study was to investigate the effect of JOINS on the pharmacokinetic (PK) profiles of aceclofenac in healthy adults. A PK drug-drug interaction study was conducted in 61 healthy subjects by using an open-label, multiple-dose, one sequence, two-period design. Blood samples were collected for plasma concentrations of aceclofenac during the reference period (aceclofenac 100 mg alone) and interaction period (aceclofenac 100 mg + JOINS 300 mg). The area under the curve within a dosing interval (τ) at steady state (AUC(τ,ss)) and the C(max) at steady state (C(max,ss)) of aceclofenac were analyzed by a non-compartment model using the Phoenix® WinNonlin® software version 6.3 (Pharsight, Mountain View, CA, USA). The 90% CIs of the geometric mean ratios (GMRs) of the AUC(τ,ss) of aceclofenac with JOINS to without JOINS (D4/D3 and D11/D3) were 0.9593–1.0130 and 0.9745–1.0291, respectively, and the corresponding values for the C(max,ss) of aceclofenac with JOINS to without JOINS (D4/D3 and D11/D3) were 0.8578–0.9795 and 0.8510–0.9717. Aceclofenac alone or co-administered with JOINS was safe and well tolerated with no serious adverse drug reactions or significant differences in the severity of adverse events (AEs) between the two treatment groups. We conclude that co-administration of aceclofenac with JOINS does not influence the PK and safety profiles of aceclofenac.

Pharmacokinetics and safety profiles of tadalafil/tamsulosin HCl fixed-dose combination capsule under fasted and fed condition in healthy volunteers

Co-administration of tadalafil and tamsulosin HCl in patients with benign prostate hyperplasia and erectile dysfunction is increasing in clinical settings. Development of fixed-dose combination (FDC) of tadalafil and tamsulosin HCl could contribute to improving patients' adherence and treatment efficacy. We evaluated the pharmacokinetics and safety profiles of a newly developed fixed-dose combination capsule of tadalafil 5 mg/tamsulosin HCl 0.4 mg in comparison with co-administration of each formulation in healthy volunteers under fasted and fed conditions. Two randomized, open-label, single-dose, two-way, crossover studies were completed in 29 subjects under fasted condition, and 33 subjects under fed condition. Serial blood sample collection for PK analysis was conducted up to 72 hours after dosing, and PK parameters were calculated using non-compartmental analysis. Geometric mean ratios and 90% confidence intervals of the C(max) and AUC(last) were used to evaluate comparative bioavailability. In both fasted and fed condition studies, the bioequivalence was established. The most common adverse drug reactions were orthostatic hypotension and headache with no statistical difference between treatment groups. All subjects with orthostatic hypotension recovered at follow-up test. Although changes in vital signs from baseline were statistically significant, there were no subjects with systolic blood pressure < 90 mmHg and there were no clinically meaningful signs or symptoms associated. FDC of tadalafil and tamsulosin HCl can be an alternative to co-administration of individual drugs for providing better compliance. Changes in blood pressure should be kept in mind when tadalafil and tamsulosin HCl are co-administered in clinical settings.

Bioequivalence and Dose Proportionality of Olmesartan Medoxomil Formulations

BACKGROUND: Olmesartan medoxomil is an angiotensin II receptor blocker commonly used in hypertension. First objective of this study was to evaluate the bioequivalence of two olmesartan formulations, Olmesartan 20 mg and 40 mg tablet (Yuhan, Pharmaceutical Corp. Seoul, Korea) as test drugs and Olmetec(R) 20 mg and 40 mg tablet (Daewoong, Pharmaceutical Corp. Seoul, Korea) as reference drugs. Second objective of this study was to evaluate the dose-proportionality of two formulations. METHODS: Two studies (20 mg, 40 mg) were conducted as a randomized, open-label, 2-period, crossover design. Each subject received one 20 mg or 40 mg tablet of the reference or test formulation of olmesartan medoxomil in each study. Blood samples were obtained during the 48-hour period after the dose in each treatment period. Wash-out period was 1 week in each study. Concentrations of olmesartan medoxomil in plasma were analyzed using a liquid chromatography system with tandem mass-spectrometric detection (LC/MS/MS). The primary pharmacokinetic parameters were Cmax (maximum concentration) and AUCt (area under the concentration-time curve from time 0 to the last sampling time). RESULTS: A total number of 40 healthy male volunteers participated in the study and 37 volunteers completed both treatment periods in 20 mg trial. All 40 participants completed both treatment periods in 40 mg trial. The 90 % CIs for the geometric mean ratios of the pharmacokinetic parameters (test:reference drug) were 0.93 ~ 1.04 for AUCt and 0.97 ~ 1.08 for Cmax in 20 mg trial. The 90 CIs were 0.94 ~ 1.02 for AUCt and 1.00 ~ 1.11 for Cmax in 40 mg trial. All parameters of two studies satisfy the range of bioequivalence criterion. CONCLUSION: The obtained results indicated that pharmacokinetic exposure to Olmesartan 20 mg and 40 mg tablet was bioequivalent to that of Olmetec(R) 20 mg and 40 mg tablet, respectively.

The Relationship between Serum Ferritin and High Sensitivity C-reactive Protein among Adults in a Health Promotion Center

BACKGROUND: More attention is given to oxidative hypothesis which causes atherosclerosis to be recognized as inflammatory response. The relationship between serum ferritin which catalyzes lipid peroxidation and high sensitivity C-reactive protein which reflects vascular inflammation was investigated among adults in a health promotion center. METHODS: The study group consisted of 297 men and women (men 86, women 211) who visited the health promotion center of a hospital in Seoul to have a health checkup from October 1, 2004 to April 1, 2005. These subjects answered the questionnares and were measured in the following; blood tests, brachial-ankle pulse wave velocity and several anthropometric measurements. Statistical analysis was performed on 111 subjects after exclusion of those subjects who were taking antihypertensive agents or antidiabetic agents, and who had acute inflammatory diseases, acute liver diseases, anemia, and who had a WBC > or =11,000x10(3)/mm3 or a serum ferritin > or =200 ug/L or a ABI (Ankle Brachial Index) <0.9. RESULTS: The average serum ferritin concentration of men against women was 132.57+/-43.12 ng/ml to 78.23+/-38.10 ng/ml which means that men have about 1.7 times as high concentration than women (P<0.001). Serum ferritin was significantly correlated with high sensitivity C-reactive protein (r=0.332). Even in multiple stepwise regression analysis, there was a independent relationship between serum ferritin and high sensitivity C-reactive protein (beta=0.138, P=0.010). When we analyzed with distinction of sex, this relationship in women was constant (beta=0.131, P=0.031), but serum ferritin in men just showed the trend of correlation with BMI (beta=9.510, P=0.059). CONCLUSION: There is a significant relationship between the increase of serum ferritin and high sensitivity C-reactive protein in healthy women; furthermore, studies in men need to be confirmed.

Survey of Alcoholic and Non-alcoholic Beverage Preference in College Students of the Chonnam Area / 대한지역사회영양학회지

This study investigated the intake of alcoholic and non-alcoholic beverages in college students. Five hundred and eighty seven students age 19-30 (432 male and 155 female) responded to the beverage consumption survey. Of the students 19.9% were freshman, 42.2% sophomore, 23% junior, and 15% seniors. Results are summarized as follows : 1) Beer and soju were the most commonly consumed alcoholic beverages by the college students. The amount of beverage normally consumed was 3 cans of beer or 1 bottle of soju. 2) There was no age related change in amount of alcoholic beverage consumed, but preference for liquor rather than beer increased with age. 3) Foods most commonly consumed prior to drinking were cooked rice and milk. 4) Following the drinking of alcoholic beverages the most commonly consumed food or beverage was cold water for both males and females. The next most commonly foods were cooked rice, instant noodles, and cola for males ; and cooked rice, milk, and fruit for females. 5) Cola and pear juice were the preferred non-alcoholic beverages for college students. Also popular among students were date juice for males and orange juice for females. Milk and non-cola carbonated beverages were not commonly consumed. This study provides information for the identification of possible alcoholic beverage related public health risks among college students.