Serum vitamin D levels in healthy urban population at reproductive age: effects of age, gender and season.

OBJECTIVE: The aim of the study was to determine the effects of age, gender and season on vitamin D status in healthy urban population at reproductive age. Also, we investigated the distribution of population into different groups regarding 25(OH)D levels. METHODS: Serum 25(OH)D levels of 21,317 participants: 5,364 men (25.1%) and 15,953 women (74.8%), aged between 18-45 years, applying to two medical centres for check-up located in the same city were retrospectively analyzed. Group I consisted of 14,720 participants (11,257 women and 3,463 men) in the first centre and Group II consisted of 6,597 participants (4,696 women and 1,901 men) in the second centre. RESULTS: The mean 25(OH)D levels did not differ between women and men in both groups: 23.4 (SD = 14.4) and 23.1 (SD = 12.6) in Group I, and 22.6 (SD = 15.9) and 23.1 (SD = 14.3) in Group II, respectively, (p > 0.05). Similar trends exhibiting lower mean 25(OH)D levels at younger ages and higher levels at later ages were observed in both groups; a seasonal variation of 25(OH)D levels was observed in both genders with the highest levels in August and September and the lowest levels from February through April; percentages of women with 25(OH)D level of < 5 ng/ml were significantly higher than of men in Group I (1.4% vs. 0.2%, respectively, p < 0.001) and in Group II (4.1% vs. 1.1%, respectively, p < 0.001). CONCLUSION: There is a slight increase in serum 25(OH)D levels from 18 through 45 years of age in healthy population. The seasonal variation of 25(OH)D levels is prominent in both genders with men having slightly lower levels in some months of winter and higher levels in summer as compared to women. The prevalence of women having 25(OH)D levels less than 5 ng/ml is higher than that of men.

Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes.

BACKGROUND: The aim of this study was to develop chitosan microspheres for nasal delivery of ondansetron hydrochloride (OND). METHOD: Microspheres were prepared with spray-drying method using glutaraldehyde as the crosslinking agent. Microspheres were characterized in terms of morphology, particle size, zeta potential, production yield, drug content, encapsulation efficiency, and in vitro drug release. RESULTS: All microspheres were spherical in shape with smooth surface and positively charged. Microspheres had also high encapsulation efficiency and the suitable particle size for nasal administration. In vitro studies indicated that all crosslinked microspheres had a significant burst effect, and sustained drug release pattern was observed until 24 hours following burst drug release. Nasal absorption of OND from crosslinked chitosan microspheres was evaluated in rats, and pharmacokinetic parameters of OND calculated from nasal microsphere administration were compared with those of both nasal and parenteral administration of aqueous solutions of OND. In vivo data also supported that OND-loaded microspheres were also able to attain a sustained plasma profile and significantly larger area under the curve values with respect to nasal aqueous solution of OND. CONCLUSION: Based on in vitro and in vivo data, it could be concluded that crosslinked chitosan microspheres are considered as a nasal delivery system of OND.

Ondansetron-loaded biodegradable microspheres as a nasal sustained delivery system: in vitro/in vivo studies.

The aim of this study was to prepare ondansetron-loaded biodegradable microspheres as a nasal delivery system. Microspheres were prepared with emulsification/spray-drying technique using poly(d,l-lactide) (PLA) and two different types of poly(d,l-lactide-co-glycolide) (PLGA). The effect of the type of organic solvent (dichloromethane (DCM) or a mixture of DCM and ethyl acetate) on the microsphere characteristics was also examined. The prepared microspheres were evaluated with respect to the morphological properties, particle size, zeta potential, drug loading efficiency, and in vitro drug release. The mean particle size (d(50)) of microsphere formulations was ranged from 11.67-25.54 µm, indicating suitable particle size for nasal administration. All microspheres had low drug loading efficiency in the range of 12.28-21.04%. The results indicated that particle size of microspheres were affected by both type of polymer and organic solvent, however drug loading efficiency of microspheres were affected by only the type of organic solvent used. All microspheres were negatively charged due to the polymers (PLA or PLGA) used. A prolonged in vitro drug release profile was observed for 96 h. Based on in vitro data, the selected microsphere formulation has been applied via nasal route to rats in vivo. Following nasal administration of ondansetron-loaded microsphere to rats, ondansetron plasma levels were within a range of 30-48 ng/mL during 96 h, indicating a sustained drug delivery pattern and relatively a constant plasma drug concentration level. The results suggested that biodegradable microspheres prepared with emulsification/spray-drying technique could be considered to deliver ondansetron via nasal route to obtain a prolonged release.

Nasal administration of heparin-loaded microspheres based on poly(lactic acid).

In this study, heparin-loaded microspheres having smooth surface and small particle size were designed in order to provide the absorption of heparin through nasal mucosa. For this purpose, microspheres at different polymer/drug ratios (1:10, 1:2.5 and 1:1) and at different concentrations of polyvinyl alcohol, emulsifying agent (1.5% and 2.5% w/v) were prepared by solvent evaporation method with poly(lactic acid). The microspheres were for evaluated shape and surface properties, particle size, production yield, encapsulation efficiency and in vitro drug release. Based on the in vitro data, selected microspheres were applied by nasal route to Wistar albino rats. According to in vivo studies, heparin-loaded microspheres may be used by nasal route as an alternative to parenteral route.

Circadian variations in exsorptive transport: in situ intestinal perfusion data and in vivo relevance.

The circadian timing system (CTS) governs the 24-h rhythm of the organism and, hence, also main pathways responsible for drug pharmacokinetics. P-glycoprotein (P-gp) is a drug transporter that plays a pivotal role in drug absorption, distribution, and elimination, and temporal changes in its activity may affect input, output, activity, and toxicity profile of drugs. In the current study, the influence of different circadian stages on the overall intestinal permeability (P(eff)) of the P-gp substrates talinolol and losartan was evaluated in in situ intestinal perfusion studies in rats. Additionally, in vivo studies in rats were performed by employing the P-gp probe talinolol during the day (nonactive) and night (active) period in rats. Effective intestinal permeabilities of talinolol and losartan were smaller in studies performed during the night (p < .05), indicating that P-gp-dependent intestinal secretion is greater during the nighttime activity span than daytime rest span of the animals. P-gp modulators vinblastine and PSC833 led to a significant decrease of talinolol and losartan exsorption in the intestinal segments as compared with control groups. Strikingly, the permeability-enhancing effect of vinblastine and PSC833 was higher with night perfusions, for both talinolol and losartan. In vivo studies performed with talinolol revealed-consistent with the in situ studies (P(eff) day > night)-a day vs. night difference in the oral availability of talinolol in the group of male rats in terms of the area under the curve (AUC) data (AUC(day) > AUC(night)). The P-gp modulator vinblastine significantly increased talinolol AUC(day) (p < .05), whereas only a weak vinblastine effect was seen in night. According to the in situ data, the functional activity of P-gp was regulated by the CTS in jejunum and ileum, which are major intestinal segments for energy-dependent efflux. In conclusion, circadian rhythms may affect carrier-mediated active efflux and play a role in the absorption process. In addition to daily rhythms in P-gp activity in rat intestine, the in vivo studies indicate that absorption-, distribution-, metabolism-, and elimination-relevant rhythms may be involved in the circadian kinetics of the drug, besides transporter-dependent efflux, such well-known aspects as metabolic or renal clearance or motility. Since this also holds true for a potentially interacting second compound (modulator), modulator effects should be evaluated carefully in transporter related drug-drug interactions.