A simple, rapid, sensitive, and reproducible LC-MS/MS method was developed for simultaneous quantification of flavoxate and 3-methyl-flavone-8-carboxylic (MFCA) in human plasma, using diphenhydramine HCl as internal standard (IS). The chromatographic separation was achieved using Agilent Poroshell 120 EC-C18 - Fast LC column (100 × 2.1mmID, 2.7 μm) fitted with UHPLC Guard Poroshell 120 EC-C18 (5 × 2.1 mmID, 2.7 μm). The mobile phase consisted of 0.1 % v/v formic acid and acetonitrile (30:70, v/v) run at a flow rate of 0.40 mL/min. The standard calibration curve was linear over the concentration range of 2.00 - 2,000.31 ng/mL and 240.00 - 24,000.04 ng/mL for flavoxate and MFCA. For flavoxate and MFCA, the within-run precision was 0.81-6.67 % and 1.68-4.37 %, while accuracy was 100.21-108.25 % and 103.99-110.28 %. The between-run precision was 2.01-9.14 % and 2.31-11.11 %, and accuracy was 96.09-103.33 % and 102.37-109.52 %. The extended run precision was 7.78-11.04 % and 2.22-3.33 %, while accuracy was 100.72-101.88 % and 102.34-105.60 %. Flavoxate and MFCA in plasma were stable 4 h at bench top (short term), 24 h in autosampler and instrumentation room (post-preparative), after 7 freeze-thaw cycles, and 89 days in the freezer. Both analytes and IS stock solutions were stable for 31 days when kept at room temperature (25 ± 4 °C) and refrigerated (2-8 °C). The validated method was successfully applied to a bioequivalence study of two flavoxate formulations involving 24 healthy volunteers.
The lower limit of soluble zinc content that can possibly be applied onto a wounded skin as a healing promoter was not known. This study examined skin wound healing process of rats inflicted by partial thickness thermal burn wound as a function of applied soluble zinc contents (0.1 ml of zinc chloride solution 0.01% (w/w) or 5.0% (w/w)). The size, surface morphology and histological profiles of wound beds of untreated rats and those treated with zinc chloride solutions were characterized. A soluble zinc content as low as 10.5 μg/cm2 of skin negated skin wound healing when compared to the untreated rats. This was alarming as the commercial products currently in the market are formulated with a high level of zinc content. Albeit the zinc salt employed was water-insoluble, a minute fraction of soluble zinc might be available to the treatment sites. This could be partially responsible for the late adverse effects such as pruritis and inflammation reported with calamine/diphenhydramine lotion, medicated shampoo, Olay Complete defense moisturizing lotion and Zineryt® topical solution. The skin irritation was likely a resultant oxidative stress action of soluble zinc, where a small fraction could be adequate to negate the skin homeostasis.[Figure: see text]Key messagesZinc is essentially a cofactor for skin collagen formation.Soluble zinc content as low as 10.5 μg/cm2 of skin irritates skin and negates burn wound healing.Skin irritation of commercial products relates to minute soluble zinc content availability.
The edema inducing activity of phospholipase A2 (PLA2) enzymes from snake venoms and porcine pancreas was investigated using mouse paw as experimental model. All ten PLA2 enzymes exhibited potent edema inducing activity. PLA2, however, is generally not the major edema inducing component of snake venom. Chemical modification studies indicated that enzymatic activity of PLA2 was required for its edema inducing activity. All PLA2 enzymes examined displayed a rapid onset edema which was suppressed by pretreatment of the mice with antihistamine. Dexamethasone pretreatment also inhibited edemas elicited by some PLA2 enzymes.
BACKGROUND: Prescribing medicines in an unlicensed and off-label manner for children is a widespread practice around the world.
OBJECTIVES: To determine the extent and predictors of off-label respiratory drug prescriptions for children in the outpatient clinics of a hospital in Malaysia.
SETTING: Outpatient clinics at the Universiti Kebangsaan Malaysia Medical Centre, a tertiary teaching hospital in Malaysia.
METHODS: The pharmacy-based computer system and medical records of the patients were utilized to collect data from 220 pediatric patients who were prescribed at least one respiratory drug from July 2011 to December 2011.
MAIN OUTCOME MEASURE: Characteristics of the off-label respiratory drug prescriptions were measured.
RESULTS: A total of 134 children (60.9 %) received at least one respiratory drug prescribed in an off-label manner. The most common reasons for the off-label prescribing of drugs were off-label use by indication (31.5 %), followed by higher than the recommended dose (24.9 %) and lower than the recommended frequency (17.1 %). Diphenhydramine was the most common respiratory drug prescribed off-label. The number of medications prescribed was the only significant predictor of off-label prescription of respiratory drugs. Pediatric patients receiving 4-6 medications were 7.8 times more likely to receive at least one off-label respiratory drug compared to pediatric patients that received 1-3 medications (OR 7.8, 95 % CI 1.74-37.44).
CONCLUSION: There was substantial prescribing of respiratory drugs for children in an off-label manner at the outpatient clinics at the Universiti Kebangsaan Malaysia Medical Centre. This highlights the need for more research to be carried out on respiratory drugs in the pediatric population.
Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
Matched MeSH terms: Diphenhydramine/therapeutic use