Tranexamic acid through intravenous,intramuscular and oral routes: an individual participant data meta‐analysis of pharmacokinetic studies in healthy volunteers

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.     

Bioavailability of intramuscularly administered tenoxicam

Bioavailability of intramuscularly administered tenoxicam relative to single oral and relative to intravenous doses was determined in two separate randomized crossover studies. Twelve healthy volunteers (12 males, age 20–30 years) received a rapid intravenous injection and a single intramuscular dose and 12 other subjects (11 males, 1 female, age 21–25 years) a single oral and a single intramuscular dose of 20 mg of tenoxicam on two different occasions. The wash-out period between the two consecutive treatments was 4 weeks. Plasma concentrations after dosing were determined by a specific HPLC method. Differences in tenoxicam concentration-time profiles after the different routes of administration were limited to the first 2 h after dosing. Later, plasma concentrations were almost superimposable within and across the two studies. The extent of absorption of intramuscularly administered tenoxicam was complete (mean ± CV per cent: F_abs 0.99 ± 20 per cent) with no difference between the two extravascular administrations (F_rel 0.95 ± 10 per cent, intramuscular vs oral). After intramuscular administration tenoxicam was more rapidly absorbed compared to the oral dose (T_max 0.71 h ± 80 per cent vs 1.4 h ± 62 per cent; p>0.05). Peak concentrations after oral and intramuscular administration (C_max 2.5 mg 1^?1 ± 19 per cent vs 2.7 mg l^?1 14 per cent; p <0.05) were very similar.     

Evacuation of hematomas using liposuction technology: Technique and literature review

Established nonexpanding hematomas can be successfully treated with minimal morbidity using standard liposucstion techniques at the bedside or in an outpatient setting under local anesthesia. The authors presents a series of eight patients and discuss current concepts of dealing with this common and distressing surgical complication.     

Failure of intramuscular antivenom in Red‐back spider envenoming

Four cases of Red‐back spider envenoming are reported in which there was minimal response to intramuscular antivenom. Intravenous antivenom was then administered in each case with almost complete resolution of symptoms. All cases were followed up to confirm the effect of treatment. This failure of intramuscular Red‐back antivenom raises the question of its efficacy. There has been no controlled trial to prove that intramuscular Red‐back antivenom is effective and animal work with other antivenoms has demonstrated the intramuscular formulation to have delayed and incomplete effects. Controlled studies should be undertaken to establish the effectiveness of intravenous and intramuscular Red‐back antivenom.     

Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity. METHODS: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.     

注射性臀肌纤维化的实验研究

以家兔为实验动物,连续肌注青霉素5天后局部水肿;10天后肌纤维混浊肿胀,纤维母细胞增生;15天后部分肌纤维进行性萎缩,结缔组织大量增生并形成挛缩束带,逐渐取代肌纤维,运动终板形态和结构改变,逐渐消失.预防方法包括分散肌注部位和局部早期热敷.     

人膈肌内神经分支分布

目的：探讨人膈的神经支配和肌内神经分支分布特点。方法：改良Sihler’s肌内神经分支染色法。结果：(1)一侧膈神经入肌后一般分为3—4支(3支型4例,4支型2例),1支(前支)向前内侧走行,支配胸部,1～2支(前外侧支)向外侧走行,支配肋部,最后1支(后支)最粗大,向后下走行,分为后外侧支和后脚支,分别支配膈中心腱外侧叶后外侧的肋部和腰部,各级神经的分支在肌束中部密集排列成神经丛。(2)6例标本均未发现左侧或右侧膈神经越过中线至对侧。(3)2例带肋间肌的标本肉眼未见有肋间神经分支进入膈。结论：(1)左、右膈神经分布于膈,未见左右侧膈神经重叠支配和优势支配。(2)膈神经的终末分支在肌束中部密集排列形成似“肾形”的神经丛带。     

肌肉注射氨甲喋呤治疗异位妊娠

[目的 ]探讨氨甲喋呤单次肌肉注射治疗异位妊娠的效果及适应症 .[方法 ]对 2 1例异位妊娠患者单次肌肉注射氨甲喋呤 ,剂量为 5 0mg/m2 ,每周检测绒毛膜促性腺激素水平 .[结果 ]17例 (80 % )成功 ,4例失败 ,成功与否与首次检测时的血绒毛膜促性腺激素值高低有关 .[结论 ]肌肉注射氨甲喋呤是简便而有效的治疗早期异位妊娠的方法之一 ,但应严格掌握适应症 .适用于异位妊娠包块直径小于 5cm、无内出血、血绒毛膜促性激素低于 16 0 0 μg/L者