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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., (© 2019 Société Française de Pharmacologie et de Thérapeutique.)

The aim of this paper was to describe the time-course of the sedative effect of rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty children (2.13 +/- 1.43 years old) were administered 75 mg/kg chloral hydrate rectally (chloralhydrat-rectiole rectal formulation, Dr Mann-Pharma Lab, Berlin, Germany), before a CT scan or an NMR imaging. Sedation was measured at specific times using a sedation score of 1-6. Patients were continuously monitored for respiratory and heart rate, systolic and diastolic blood pressures, and oxygen saturation. About 82.35 and 94.11% of the patients had a score of sedation > or = 3 within 15 and 30 min, respectively. The mean time to effective sedation (score > or = 3) was of 0.30 +/- 0.14 h (median time, 0.25 h). The mean duration of effective sedation (score > or = 3) was 1.29 +/- 1.05 h (median duration, 0.75 h). A total of 93.1% of the X-ray sections were obtained without artifact and sedation was considered by radiologists to be efficient for 83.3% of the procedures. This sedation procedure appeared efficient and safe during ambulatory CT scan and NMR imaging. The long-term effect of chloral hydrate, however, remains to be evaluated.

Currently available tocolytic agents have shown partial or transient efficacy on uterine contractions delaying delivery for 24 or 48 h without reduction in perinatal morbidity and mortality. These facts led us to study a new tocolytic compound. A double-blind dose finding study of the nitroglycerin tocolytic effect during preterm labor was conducted using a continual reassessment method among six different doses (0.2-1.2 mg/h for 2 h) in pregnant women who were unresponsive, intolerant to salbutamol, or with a contraindication to this therapy. Twenty-five pregnant women were included. The probability of success in stopping uterine contractions reached, for the maximal dose (1.2 mg/h), only a 54% rate (95% CI: 29-79%). Twelve patients complained of headaches and 16 experienced a decrease in arterial blood pressure suggesting that it would not be safe to increase the dose in order to obtain a higher success rate. The present study suggests that nitroglycerin is not as effective as expected in controlling uterine contractions during severe preterm labor in patients where beta2 agonists cannot be used.

Diarrhea is only one of the many manifestations of intestinal parasites. Environmental influences are inescapable, regardless of an individual's state of health: in a highly endemic region, intestinal parasitic colonization is almost the rule. The clinical expression of the parasitoses, however, is largely determined by host defenses; and when they are weakened, parasitic diarrhea is frequent and severe. Protein-energy malnutrition is by far the most important cause of immune deficiency in developing countries. Diarrhea caused by Strongyloides or Giardia is common and severe in malnourished children, while well-nourished children remain healthy carriers. These parasites require specific treatment in the malnourished; and the well-nourished should have preventive treatment when they are to receive corticosteroids or immunosuppressive agents. Diarrhea caused by Cryptosporidium spp. may be severe in malnourished or immunodeficient children, and recovery is achieved only after renutrition or treatment of the immunodeficiency.

The pharmacokinetics of isoniazid (INH) was studied in children (0-196 months old) according to their acetylator phenotype, estimated from the metabolic acetyl INH/INH molar plasma concentration ratio (MR) measured 3 h after INH oral administration. There were 17 slow (MR < 0.48) and 17 fast acetylators (MR > or = 0.48). The mean apparent plasma clearance was significantly lower, the mean apparent volume of distribution higher and the half-life longer in the slow acetylator group (C1, 0.298 +/- 0.099 L/h/kg; Vd, 1.56 +/- 0.65 L/kg; t1/2, 3.88 +/- 01.89 h) than in the fast acetylator group (Cl, 0.528 +/- 0.234 L/h/kg; Vd, 1.06 +/- 0.45; t1/2, 1.64 +/- 1.1 h). The half-life decreased with age. An impaired isoniazid elimination was suggested in children less than three months old, which may be in favour of an individual dose adjustment in this population.