Two-Hour Nasal Responses after a Single Dose of Ephedrine Nasal Spray in Healthy Males.

Background: Ephedrine is often used as nasal decongestant. Yet, the clinical study of intranasal ephedrine is scarce. In addition, the study tools may affect the measurement of the nasal patency. This problem has not been concerned. Objective: To investigate the nasal responses after using a single-dose of calibrated ephedrine nasal spray in Thai healthy male volunteers. The study also compared the differences between two methods of nasal patency measurement. Material and Method: Healthy males (n = 20) were recruited in a randomized, crossover, 2-day study. Each day was studied for anterior rhinomanometry (RN) or peak nasal inspiratory flow (PNIF). On test day, subjects were given ephedrine nasal spray, and measured by the specific tool for two hours. In addition, the visual analogue scale (VAS), cardiovascular (CVS) parameters, and adverse drug reactions were examined. Results: A single-dose ephedrine nasal spray significantly changed the nasal airway resistance (NAR), PNIF, and VAS at 5-minute. The NAR via RN was maximally decreased by 43.74±16.3% at 10-minute and returned to baseline at 90-minute. While, PNIF was maximally increased by 31.20±18.4% at 10-minute and returned to baseline at 60-minute. The nasal responses measured by two methods were significantly different at 5-, 15-, and 45-minute. VAS for nasal patency showed significant increases throughout the study period. CVS effects were negligible. Bitter taste was the most common adverse event reported. Conclusion: Ephedrine nasal spray is a fast-onset, short-acting decongestant. The decongestant effect of the drug varied by study tools. The variations appeared on the degree of nasal response and duration of action. The drug was generally safe.

Effects of the Chinese Herbal Formulation (Liu Wei Di Huang Wan) on the Pharmacokinetics of Isoflavones in Postmenopausal Women.

A combination of soy isoflavones and Liu Wei Di Huang Wan (LWDHW) is potentially effective for postmenopausal women with intolerable vasomotor episodes who are not suitable candidates for hormonal therapy. The objective of this open-label, three-phase, crossover study was to determine the influence of both single and multiple oral doses of LWDHW on isoflavone pharmacokinetics in healthy postmenopausal women. Eleven subjects were assigned to receive the following regimens in a fixed sequence with washout periods of at least one week: Phase A, a single oral dose of soy milk; Phase B, a single oral dose of soy milk coadministered with LWDHW; and Phase C, multiple oral doses of LWDHW for 14 days followed by a single oral dose of soy milk. Blood samples were collected and mixed with ß-glucuronidase/sulfatase to hydrolyze isoflavone conjugates to their respective aglycones (i.e., daidzein and genistein) and were determined using high performance liquid chromatography. The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). The results found no statistically significant differences in pharmacokinetic parameters of daidzein and genistein among the three regimens.

Effect of synbiotic fermented milk on oral bioavailability of isoflavones in postmenopausal women.

The purpose of this study was to investigate the effect of synbiotic fermented milk, containing Lactobacillus paracasei and inulin, on oral bioavailability and pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a one-group pre-post treatment study. Twelve subjects were assigned to consume a single oral dose of 375 mL of soy beverage. Blood samples were collected immediately before and at various time points until 32 hours after the administration of the soy beverage. After a washout period, subjects were requested to consume 180 mL of synbiotic fermented milk after breakfast and dinner for 14 days, followed by a single oral dose of 375 mL of soy beverage on the next day. Collection of blood samples after the administration of the soy beverage were performed at the same time points as the former phase. Plasma isoflavone concentrations were measured by using high-performance liquid chromatography (HPLC) technique. In conclusion, this study highlighted that continuous consumption of synbiotic fermented milk followed by a single oral administration of soy beverage significantly enhanced oral bioavailability of isoflavones compared with a single oral dose of soy beverage alone.

Bioequivalence study of modified-release gliclazide tablets in healthy volunteers.

This study was aimed to investigate bioequivalence of modified-release 30 mg gliclazide tablets in 18 healthy Thai volunteers. A test product, Glycon MR (Siam Bheasach, TH), was compared with a reference product, Diamicron MR (Servier, France). The study was performed under a single-dose, two-treatment, two-period, and two-sequence crossover design in fasted and fed conditions with a washout period of 2 weeks. Blood samples were collected for 72 h after drug administration. Drug plasma concentrations were determined by HPLC with a UV detector. Analysis of pharmacokinetic characteristics was based on a non-compartmental model. The logarithmically transformed data of C(max) and AUCs were analyzed for 90% confidence intervals using ANOVA. The test product gave slightly higher C(max) in both conditions and shorter T(max) in the fed condition. However, there is no significant difference in pharmacokinetic characteristics between both products under fasted and fed conditions. Effect of food was not significantly observed. The 90% confidence intervals were within the acceptance criteria of 0.80-1.25 regardless of the food effect, indicating bioequivalence between the two products on the rate and extent of gliclazide MR absorption without regard to meals.

Influence of fructooligosaccharide on pharmacokinetics of isoflavones in postmenopausal women.

The objective of the present paper was to determine the influence of fructooligosaccharide (FOS) on the pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a fixed-sequence, two-phase, crossover study. Twelve subjects received a single oral dose of 300 mL of a soy beverage. Blood samples were collected before the dose and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 32 h after the administration of the soy beverage. After a washout period of at least 1 week, subjects were assigned to receive oral doses of FOS, 5 g each time, twice a day (after breakfast and dinner) for 14 days, followed by a single oral dose of the same soy beverage on the next day. Blood samples were then collected at the same time points mentioned previously. Plasma isoflavone concentrations were determined by HPLC. Continuous oral administrations of FOS followed by a single oral administration of soy beverage caused significant increases in C(max), AUC(0-32), and AUC(0-∞) of genistein and AUC(0-32) of daidzein, comparing to those obtained following a single oral dose of soy beverage alone. Other pharmacokinetic parameters (T(max) and t(1/2) of both aglycones and AUC(0-∞) of daidzein) between both regimens were not significantly different.

Effects of vitamin d plus calcium supplements on pharmacokinetics of isoflavones in thai postmenopausal women.

The objective of this study was to determine the effects of vitamin D(3) plus calcium supplements (D(3)-calcium) on pharmacokinetics of isoflavones in Thai postmenopausal women. This study was an open-labeled, randomized three-phase crossover study. Twelve healthy subjects were randomized to receive one of the following regimens: (a) a single dose of isoflavones, (b) a single dose of isoflavones, and D(3)-calcium, or (c) continuous D(3)-calcium for 7 days followed by a single dose of isoflavones on the 8th day. After a washout period, subjects were switched to receive the 2 remaining regimens according to their randomized sequences. Blood samples were collected before dose and at specific time points until 32 hours after isoflavone administration. Plasma was treated with ß-glucuronidase/sulfatase to hydrolyze glucuronide and sulfate conjugates of daidzein and genistein. Plasma concentrations of daidzein and genistein were determined by high performance liquid chromatography. The estimated pharmacokinetic parameters of isoflavones were time to maximal plasma concentration (T(max)), maximal plasma concentration (C(max)), half-life (t(1/2)) and area under the plasma concentration-time curve (AUC). T(max) of daidzein and genistein after regimen B was significantly longer than that of regimen A. Other pharmacokinetic parameters of daidzein and genistein obtained following the three regimens were not significantly different.