Prevalence of hypovitaminosis D and folate deficiency in healthy young female Austrian students in a health care profession.

PURPOSE: We performed a single-day cross-sectional study to assess the prevalence of vitamin D deficiency as well as folate status in healthy young female volunteers well educated with respect to health information. METHODS: We assessed dietary intake of vitamin D and calcium, serum concentrations of 25-OH-vitamin D(3), folate, red blood cell folate and other dietary, laboratory, and lifestyle parameters in 215 young healthy women (age 18-30 years) on a single day at the end of the winter months. Primary aim was to investigate the prevalence of hypovitaminosis D. Folic acid status was a secondary study aim. RESULTS: Mean daily ingestion of vitamin D was 2.25 µg/day with a daily calcium intake of 749 mg/day. 6.9% had hypovitaminosis D (25-OH-vitamin D(3) <30 nmol/L) and 89.3% were vitamin D insufficient (<75 nmol/L). Preplanned subpopulation comparison (lower vs. upper quartile) revealed a significant negative correlation (P = 0.048) between plasma PTH and 25-OH-vitamin D(3) levels. Fifteen individuals (6.9%) were folic acid deficient (<140 ng/mL RBC folate). Only 9.3% reached RBC folate concentrations regarded as optimal for the prevention of fetal neural tube defects (>400 ng/mL). CONCLUSIONS: The prevalence of hypovitaminosis D in healthy young women trained in health care professions is low but 89.3% can be classified as vitamin D insufficient in spring. Folate status can also be considered not sufficient. Considering the emerging role of higher vitamin D plasma levels for many health conditions, a timely correction of vitamin D status in the general Austrian population appears appropriate.

Sinoaortic denervation abolishes blood pressure-induced GABA release in the locus coeruleus of conscious rats.

Male Sprague-Dawley rats underwent sinoaortic denervation (SAD) or sham operation. We examined changes in the release rates of GABA, glutamate and arginine in the locus coeruleus (LC) elicited by experimental blood pressure increases (i.v. noradrenaline infusion for 3 min, 4 microg kg(-1)min(-1)) or decreases (i.v. sodium nitroprusside infusion for 3 min, 150 microg kg(-1)min(-1)). The release of the neurotransmitters was monitored by the push-pull superfusion technique. Mean blood pressure did not differ between sham-operated and SAD rats but blood pressure lability was greatly enhanced in SAD rats and accompanied by increased basal release of glutamate in the LC. GABA release was not affected. A rise in blood pressure induced by noradrenaline enhanced GABA release in the LC of sham-operated rats. This effect was abolished by SAD. Glutamate release did not respond to hypertension either in SAD or in sham-operated rats. Nitroprusside led to a fall in blood pressure which was more pronounced and lasted longer in SAD than in sham-operated rats. In SAD rats, glutamate release was enhanced by nitroprusside. The depressor response had no effect on glutamate release in sham-operated rats. GABA release did not respond to this stimulus in either SAD or sham-operated rats. SAD and blood pressure changes did not influence the release rate of arginine. In conclusion, experimental hypertension increases GABAergic activity in the LC by stimulating peripheral baroreceptors. In SAD rats, augmented blood pressure lability seems to be at least partly due to elevated glutamate outflow within the LC.

Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in neurointensive care patients with staphylococcal ventriculitis associated with external ventricular drains.

The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five neurointensive care patients with staphylococcal ventriculitis was studied. The mean area under concentration-time curve (+/- standard deviation) was 63 +/- 18.9 mg x h/liter, with a CSF-to-plasma ratio of 0.8 +/- 0.3. Times above MIC in CSF were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter, respectively.

A bioequivalence study of two oral desmopressin tablet formulations.

The present study was carried out to test bioequivalence between two different oral desmopressin formulations. Sixty healthy volunteers were enrolled in the study and were randomly assigned to receive the test (T) and reference (R) drug in a two-period two-sequence, crossover, analyst-blinded study design. Subjects received an oral dose of 400 mug of desmopressin acetate separated by a wash-out period of at least 7 days. The area under the concentration-time curve (AUC) over 12 h in plasma and the maximum concentration (C(max)) were compared by analysis of variance (ANOVA) after log transformation. The mean ratios of the T to R drug were within the bioequivalence boundaries with mean values of 1.00 (90% CI: 0.87-1.14) and 1.03 (90% CI: 0.92-1.15) for AUC(0-t) and AUC(0-inf), respectively. For the C(max), the mean ratio of the T to R drug was 0.97 (90% CI: 0.87-1.08). The rate and the extent of oral desmopressin absorption were identical for both formulations. Hence, the desmopressin test tablet met all bioequivalence criteria of the marketed reference desmopressin tablet.

A replicate study design for testing bioequivalence: a case study on two desmopressin nasal spray preparations.

OBJECTIVE: The present study was carried out to test bioequivalence between two different desmopressin nasal spray preparations. Due to the high variability of plasma pharmacokinetics of intranasally administered peptides like desmopressin, appropriate study designs are required to assess bioequivalence. Therefore, a single-dose, replicate study design was used to evaluate bioequivalence of two desmopressin nasal sprays. SUBJECTS AND METHODS: Thirty-two healthy male volunteers were enrolled in the study and were randomly assigned to receive the test- and reference drug on two occasions in a 4-period 2-sequence crossover study design. Subjects received a single dose of 20 microg (10 microg per nostril) of desmopressin-acetate per study day separated by wash-out periods of at least 1 week. Desmopressin blood concentrations were measured serially over a 14-h period using a validated radioimmunoassay method. Statistical analysis was initially performed using a complicated mixed-analysis model testing for individual bioequivalence according to recommendations by the Food and Drug Administration. This approach, however, failed to converge with all defined main PK parameters and, thus, a traditional mixed analysis of variance analysis based on population averages was definitely used for testing bioequivalence between study drugs. The procedure of selecting an appropriate statistical analysis for a replicate study design was predefined in the study protocol. RESULTS: The 90% confidence intervals (CI) were calculated for the area under the time-concentration curve (AUC), maximum concentration (C(max)) and the time to reach C(max) (t(max)) of test/reference drug ratios for a bioequivalence range from 0.80-1.25. The mean test/reference drug ratios were completely within the 90% CIs with values of 1.041 (CI: 0.892-1.216), 1.021 (CI: 0.913-1.140) and 1.068 (CI: 0.914-1.249) for AUC(0-14 h), C(max) and t(max), respectively. CONCLUSION: The rate and the extent of intranasal desmopressin absorption are identical for both study preparations. Thus, the desmopressin test preparation met all equivalence criteria and thereby was proven bioequivalent with a marketed reference nasal desmopressin spray.