Pharmacokinetics of a telmisartan, amlodipine and hydrochlorothiazide fixed-dose combination: A replicate crossover study in healthy Korean male subjects

Purpose: To compare the tolerability and pharmacokinetic profiles of telmisartan, amlodipine, and hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC, test product) with a co-administered telmisartan/amlodipine FDC and HCTZ in a single-entity tablet (reference product)Methods: This was a single-dose, randomized, open-label, replicate crossover study conducted in healthy male Korean volunteers aged 19 – 50 years. Fasting randomized subjects received a newly developed test product (telmisartan/ amlodipine/HCTZ, 80/10/25 mg) or two tablets of Twynsta® (40/5 mg) and one tablet of HCTZ (25 mg) as reference products. After a washout period, each group replicated the exposure of the other group.Results: The AUClast (h•ng/mL) geometric mean was 3,194.87 and 3,273.77 for the telmisartan test and reference products, respectively; 329.92 and 315.13 for the amlodipine test and reference products; 1,203.98 and 1,150.86 for the HCTZ test and reference products, respectively. The geometric mean of Cmax (ng/mL) was 543.04 and 497.81 for the telmisartan test and reference products, respectively; 7.74 and 7.34 for the amlodipine test and reference products; 218.71 and 184.39 for the HCTZ test and reference products, respectively. For telmisartan, the 90 % CI of GMRs of AUClast (h•ng/mL) and Cmax (ng/mL) were 0.9414 – 1.0496 and 1.0246 – 1.2792, respectively; the coefficient of variation (CV) of telmisartan Cmax was 41.96 %.Conclusion: A formulated FDC tablet containing a telmisartan/amlodipine/HCTZ combination (80/10/25mg) was bioequivalent to a co-administrated commercially available telmisartan/amlodipine combination and HCTZ tablets at equivalent concentrations.Keywords: Fixed-dose combination, Hypertension, Telmisartan, Amlodipine besylate, Hydrochlorothiazide, Pharmacokinetic

Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis

Oral Muscle Relaxant May Induce Immediate Allergic Reactions

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully

Compartment syndrome due to extravasation of peripheral parenteral nutrition: extravasation injury of parenteral nutrition

Compartment syndrome is a rare but devastating condition that can result in permanent neuromuscular or soft tissue injuries. Extravasation injuries, among the iatrogenic causes of compartment syndrome, occur under a wide variety of circumstances in the inpatient setting. Total parenteral nutrition via a peripheral route is an effective alternative for the management of critically ill children who do not obtain adequate nutrition via the oral route. However, there is an inherent risk of extravasation, which can cause compartment syndrome, especially when detected at a later stage. Herein, we report a rare case of compartment syndrome and skin necrosis due to extravasation, requiring emergency fasciotomy and skin graft in a 7-month-old boy who was treated with peripheral parenteral nutrition via a pressurized infusion pump. Although we cannot estimate the exact time at which extravasation occurred, the extent and degree of the wound suggest that the ischemic insult was prolonged, lasting for several hours. Pediatric clinicians and medical teams should carefully examine the site of insertion of the intravenous catheter, especially in patients receiving parenteral nutrition via a peripheral intravenous catheter with a pressurized infusion pump

Dining-out behaviors of residents in Chuncheon city, Korea, in comparison to the Korean National Health and Nutrition Survey 2001

Dining-out behavior is associated not only with socio-demographic characteristics such as gender, education, occupation, residence, and marital status, but also with individual preferences, such as eating-out activities, interests, and opinions. We investigated dining-out behaviors and their associated factors. Announcements by health practioners and the Chief of Dong Office were used to recruit 739 residents (217 males and 522 females) in Chuncheon, Korea. Information on the frequency and reasons for eating out, the standards for meal selection, and the overall satisfaction with restaurants, based on taste, nutrition, amount, price, service, sanitation, and subsidiary facilities of restaurants, was obtained through personal interviews with a structured questionnaire. Among all respondents, 46.3% of subjects ate outside of the home once or twice a month, and 33.8% reported that they ate out only a few times a year, or never. This was much higher than the national average of 52.0% as reported by the Korean National Health and Nutrition Survey (KNHNS) in 2001. The frequency of eating out differed significantly according to age (p=0.001), family income (p<0.001), residential area (p<0.001), and educational level (p<0.001). The most common reasons for dining out were meetings (46.7%), followed by special celebrations (15.4%), and enjoyment (11.2%). Korean food (55.3%) was the most frequently selected type of meal when eating out, and food was most often selected based on personal preferences (41.4%) and taste (29.8%); only 5.5% and 7.7% of subjects considered nutrition or other factors (e.g., sanitation), respectively. The results showed that the frequency of eating out for Chuncheon residents was much lower than the national average; in addition, eating-out behaviors depended on the residents' socio-demographic and personal characteristics

A Case of Familial Juvenile Hyperuricemic Nephropathy with Novel Uromodulin Gene Mutation, a Novel Heterozygous Missense Mutation in Korea

Familial Juvenile hyperuricemic nephropathy (FJHN, OMIM #162000) is a rare autosomal dominant disorder characterized by hyperuricemia with renal uric acid under-excretion, gout and chronic kidney disease. In most but not all families with FJHN, genetic studies have revealed mutations in the uromodulin (UMOD) gene located on chromosome 16p11-p13. We here described a novel heterozygous missense mutation (c.1382C>A causing p.Ala461Glu) in an affected 16-year-old male with hyperuricemia, gout and chronic kidney disease. His father was also affected and the UMOD mutation was found to segregate with the disease. There has been only one case report of Korean family with FJHN, which has not been diagnosed by genetic study. This is the first report of genetically diagnosed FJHN in Korea