Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences

Background

The diuretic effect of valproates and its relation to urinary potassium (K⁺) and chloride (Cl^-) excretion have not yet been investigated, so the aim of this study was to evaluate the influence of a single dose of sodium valproate (NaVPA) on 24-h urinary K⁺ and Cl^- excretion in young adult Wistar rats of both genders. For measurement of K⁺ in urine, the same animals and samples as in our earlier publication were used (Pharmacology 2005 Nov, 75:111–115). The authors propose a new approach to the pathophysiological mechanisms of NaVPA effect on K⁺ and Cl^- metabolism. Twenty six Wistar rats were examined after a single intragastric administration of 300 mg/kg NaVPA (13 NaVPA-male and 13 NaVPA-female), 28 control intact Wistar rats (14 males and 14 females) were studied as a control group. The 24-h urinary K⁺, Cl^-, creatinine and pH levels were measured.

Results

Total 24-h diuresis and 24-h diuresis per 100 g of body weight were found to be significantly higher in NaVPA-rats of both genders than in rats of the control group (p < 0.05). The data showed NaVPA to enhance 24-h K⁺ excretion in NaVPA-males and NaVPA-females with significant gender-related differences: 24-h K⁺ excretion in NaVPA-male rats was significantly higher than in control males (p = 0.003) and NaVPA-female rats (p < 0.001). Regarding the 24-h K⁺ excretion, NaVPA-female rats did not show a statistically significant difference versus females of the control group (p > 0.05). 24-h urinary K⁺ excretion per 100 g of body weight in NaVPA-male rats was significantly higher than in control males (p = 0.025). NaVPA enhanced Cl^- urinary excretion: 24-h Cl^- urinary excretion, 24-h urinary Cl^- excretion per 100 g of body weight and the Cl^-/creatinine ratio were significantly higher in NaVPA-male and NaVPA-female rats than in gender-matched controls (p < 0.05). 24-h chloriduretic response to NaVPA in male rats was significantly higher than in female rats (p < 0.05).

Conclusion

NaVPA causes kaliuretic and chloriduretic effects with gender-related differences in rats. Further investigations are necessary to elucidate the mechanism of such pharmacological effects of NaVPA.     

Sex-related differences in urinary excretion of egualen sodium in rats.

Egualen sodium (sodium 3-ethyl-7-isopropyl-1-azulenesulfonate 1/3 hydrate) is a new antiulcer drug. There has been no difference observed in absorption between male and female rats, the relative amount of metabolites in male plasma has been higher than that in females, and the excretion ratios of metabolites in males have been significantly higher than those in females. However, the plasma concentration profile of total radioactivity in males has been higher than that in females. To clarify this discrepancy, the renal clearances and plasma concentrations of the unchanged drug and its metabolites were determined. The renal clearance of the unchanged drug in males was 21 times lower than that in females, and the urinary excretions in males and females were 2.1 and 39.5% of dose, respectively. This indicates that the major factor in the sex-related difference observed in the plasma concentration of total radioactivity is due to the difference in the renal clearance of the unchanged drug between the sexes. The results of treatments with probenecid in normal and gonadectomized rats revealed that egualen sodium was mainly excreted into urine by secretion through the renal tubule. Furthermore, the results of treatments with testosterone in rats revealed that the excretion of egualen sodium was highly affected by androgens. These facts indicated that the sex-related difference observed in the plasma concentration of total radioactivity can be attributed to the inhibition of renal tubular secretion of the unchanged drug by androgens. This is the first example of sex-related differences in both metabolism and excretion.     

Kidney concentrations and urinary excretion of mercury,zinc and copper following the administration of mercuric chloride and sodium selenite to rats

The effect of single (SC) administration of mercuric chloride (1 mg Hg/kg) alone or jointly with (PO) sodium selenite (0.39 mg Se/kg) on kidney disposition of mercury (Hg) and metallothionein (MT) and urinary excretion of Hg, zinc (Zn) and copper (Cu) has been studied in the female rat. The excretion of Hg and essential metals was determined every day following exposure. Daily excretion of endogenous Cu and Zn the Hg-exposed group was about threefold and fourfold, respectively, in comparison with control groups of rats. Sodium selenite prevented the urinary excretion of endogenous Cu and partly of Zn.     

Effect of selenium on blood pressure,urinary sodium excretion and plasma aldosterone in cadmium-treated male rats

The present study was carried out to help elucidate the possible mechanisms underlying the effect of Cd and the interaction of Se with Cd on blood pressure. Male Wistar rats were divided into four groups: control, Cd-treated, Se-treated, Se-and Cd-treated. Cd and Se were administered at doses of 1.0 mg/kg body weight by subcutaneous injection of aqueous solutions of CdCl₂·2×1/2 H₂O and Na₂SeO₃, respectively. Injections were made either alone or in the Cd+Se treated group, simultaneously at 12–h intervals for 7 consecutive days. All animals were then maintained without further treatment for an additional period of 18 days. Treatment with Cd and Se separately lowered the blood pressure on days 3 and 8, but these levels increased and were significantly higher than that in control rats by day 26. Plasma aldosterone concentrations increased and urinary Na excretion decreased from day 1 to 3 in rats treated with Cd and Se separately. Thereafter, increased water retention precedes the onset of increased blood pressure. From these findings, we suggest that in rats treated with Cd and Se separately the increase in plasma aldosterone is a main factor for decreased urinary Na excretion and increased retention of water, and these factors may be associated with an increase in blood pressure. The treatment with Cd and Se simultaneously decreased urinary Na excretion and increased the plasma aldosterone concentration and water retention before the onset of increased blood pressure. These findings suggest that the increase in the blood pressure in these rats might be the result of the same mechanisms as in the rats treated with Cd alone. Se administered simultaneously with Cd ameliorates the Cd-induced decrease in blood pressure on days 3 and 8 but did not ameliorate the Cd-induced increase in blood pressure on day 26. The Cd concentration in the serum of rats treated with Cd and Se simultaneously was markedly higher than that in the serum of rats treated with Cd alone on day 3, suggesting that a Cd–Se complex in serum would be formed. The effect of Se in preventing a Cd-induced decrease in blood pressure may be associated with the formation of a Cd-Se complex in the serum on day 3. On the other hand, after termination of treatment with Cd and Se there was no significant difference in the Cd concentrations in the serum between the rats treated with Cd alone and the rats treated with Cd and Se together. These findings suggest that a Cd–Se complex formed in serum on day 3 might be dissociated by day 26.     

Increased urinary calcium and magnesium excretion in rats injected with mercuric chloride.

Mercuric chloride (HgCl2) is a classic nephrotoxic agent. While it is well established that HgCl2 can induce metallothionein synthesis in the kidney and also cause damage to the pars recta region of the renal tubule, the urinary losses of essential elements like calcium (Ca) and magnesium (Mg) probably related to this process, have not been described. In this study, calcium, magnesium, metallothionein (MT), as well as sodium (Na) and potassium (K) in urine, kidney cortex and liver were measured in male Wistar rats after two daily injections of HgCl2 (0.5 or 1.0 mg Hg/kg body weight intraperitoneally). As compared with controls, there was a significant 3-4-fold increase in calcium excretion which reached its maximum at 8-12 and 32-36 hr after treatment with 1.0 mg Hg/kg. Urinary magnesium excretion was also increased in a similar way as the calcium excretion. At 12-16 hr, urinary magnesium in the 1.0 mg Hg/kg dose group was 3.4 times higher than that of the controls. Urinary MT level in HgCl2 treated rats was much higher than that in the controls, the maximum excretion was between 24-28 and 32-36 hrs preceeded by the peak of Hg in urine. Na and K concentrations in urine decreased significantly in rats treated with HgCl2. The present study thus demonstrates that increases of urinary calcium and magnesium excretion are early toxic effects of HgCl2 on the kidney. It gives support to the hypotheses implying these ion imbalances in the mechanism of elicitation of renal toxicity by mercury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of theophylline on urinary excretion of total, free and acyl carnitine in rats.

BACKGROUND: Carnitine plays a critical role in lipid metabolism. Carnitine deficiency may adversely affect the oxidation of fatty acids and further aggravate abnormal lipid metabolism. OBJECTIVE: To investigate the effect of oral theophylline administration on urinary excretion of total (TC), free (FC), acyl (AC) carnitine as well as the ratio of AC to FC in rats. METHOD: The study was a randomized, controlled animal study. Theophylline was given at 100 mg/kg b.w./day and effects were monitored after a treatment period that lasted between one week and five weeks. RESULTS: Theophylline treatment caused significantly increased food intake and urinary excretion as compared to either control or placebo, P < 0.01. The results indicated that a significant increase in urinary TC, FC and AC excretion as compared to those of control and placebo groups (P < 0.01). Furthermore, the ratio of AC to FC was significantly increased (P < 0.01) as compared to either control or placebo group. CONCLUSION: Theophylline administration to rats leads to significant changes in the urinary excretion of carnitine. These changes may result from theophylline-affected alteration renal tubular re-absorption of carnitine.     

Influence of age, gender, body weight and valproate comedication on quetiapine plasma concentrations

Quetiapine is a second-generation antipsychotic with a favourable risk/benefit profile that is increasingly used in psychiatric patients. Similar to other antipsychotics, the efficacy and adverse effects of quetiapine depend much more on the actual plasma concentration of the active drug than on the prescribed dose. The present study investigated whether age, gender, body weight or certain comedications influence quetiapine plasma concentration by determining quetiapine plasma levels by tandem mass spectrometry in 94 (36 male and 58 female) patients aged 42.2 +/- 20.0 years. Older age was a significant predictor of a higher quetiapine plasma concentration, with a mean increase of weight-corrected concentration/dose ratio of 11% per 10 years of age (P = 0.003). In females, the concentration/dose (C/D) ratio was 35.4% higher than in males (adjusted mean 0.144 ng/ml/mg for males versus 0.195 ng/ml/mg for females, respectively; P = 0.035). However, after correction for weight, the gender difference in C/D ratio dropped to 22% and significance was lost (P = 0.133). Valproate comedication was associated with a 77% increase in quetiapine plasma levels (P = 0.016). In conclusion, older age, body weight and comedication with valproate have to be considered when prescribing quetiapine. Higher plasma levels in female patients need to be replicated in larger samples.     

Effects of a new pteridine derivative on urinary sodium, potassium and magnesium excretion in conscious saline-loaded rats.

1. Two recently synthesized pteridine derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.     

Reproductive toxicity of sodium valproate in male rats

Objectives:

To assess the effects of sodium valproate on rat sperm morphology, sperm count, motility, and histopathological changes in testis.

Materials and Methods:

Male Wistar rats (12 week old) were treated with sodium valpraote and sacrificed at the end of 2^nd, 4^th, 5^th, 7^th, 10^th and 15^th week after the last exposure to sodium valproate. Epididymal sperm count, sperm motility, sperm morphology, and histopathology of testes were analyzed.

Results:

Sperm count and sperm motility were decreased significantly by sodium valproate. The percentage of abnormal sperms increased in a dose-dependent manner. A histopathological study revealed that sodium valproate had caused sloughing of epithelial cells in testes.

Conclusion:

Sodium valproate causes reversible change in sperm motility, sperm count, morphology, and cytoarchitecture of testes.     

Influence of repeated administration of lithium on urinary excretion of prostaglandins in rats.

The present study was undertaken to examine whether urinary excretions of prostaglandins increase by repeated administration of a non-toxic dose of lithium. Our previous study demonstrated that 2 mEq/kg/day of lithium chloride (LiCl) is not a toxic dose; and therefore, this dose of LiCl in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 7 days into Wistar rats. On day 7, 3% body weight of 1% NaCl solution was given orally; and urine for the determination of PGE2 and 6-keto-PGF1 alpha, a metabolite of PGI2, was collected for 6 hr after dosage. Thereafter, blood samples for measuring plasma renin activity (PRA) were obtained. The urinary amounts of PGE2 and 6-keto-PGF1 alpha in the Li-treated rats were significantly greater than those in the control animals. The values of PRA did not significantly differ between the two groups of rats. These findings indicate that the production of prostaglandins, including those of PGE2 and PGI2, are enhanced during repeated administration of a non-toxic dose of lithium. The enhanced production of prostaglandins might not be mediated through the activated renin-angiotensin system.     

The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Dietary sodium intake: influence on calcium channels and urinary calcium excretion in spontaneously hypertensive rats.

Binding of the 1,4-dihydropyridine [3H]PN200 110 was employed as an index of cardiac Ca2+ channels in normotensive (WKY) and spontaneously hypertensive (SHR) rats during 4 weeks of normal (0.73% NaCl) and high (8% NaCl) sodium diets when the rats were between 20 and 24 weeks of age. Binding site density was not different at the beginning of the study but was increased significantly (P less than 0.01) after 1 week in the SHR on a high sodium diet; this difference was not apparent at 2, 3 or 4 weeks of the diet. During this same period, the urinary Ca2+ excretion in SHR was enhanced significantly (P less than 0.01) and the urinary calcium/sodium ratio was elevated during the high sodium intake period.     

The effect of potassium dichromate and mercuric chloride on urinary excretion and organ and subcellular distribution of [203Hg]mercuric chloride in rats

The mechanism by which subthreshold/non-effective doses or concentrations of potassium dichromate (K2Cr2O7) potentiate the effect of moderately effective dose/concentrations of mercuric chloride (HgCl2) on renal organic ion transport is not understood. To investigate this effect, the rate of excretion of mercury from the intact animal and the renal and hepatic accumulation and subcellular distribution of mercury within kidney cortex following pretreatment or in vitro exposure to K2Cr2O7 were undertaken. Coincidental administration of K2Cr2O7 had no significant effect in altering the rate of excretion of labeled mercury. Organ distribution showed time dependence; however, the presence of K2Cr2O7 did not increase renal mercury concentrations. In fact, significantly less mercury was found at 4 h in the kidneys of rats receiving both metal salts. Subcellular distribution of labeled mercury (203Hg) was also not significantly altered by the presence of K2Cr2O7, although the distribution patterns for in vitro exposure and pretreated tissues were different. These studies show that K2Cr2O7 does not produce alterations in urinary elimination, organ distribution or subcellular distribution of mercury.     

丙戊酸钠对大鼠碳酸锂血清水平的影响

目的探讨丙戊酸钠对碳酸锂血清水平的影响。方法20只大鼠,♀♂各半,随机分成2组,每组各10只。研究组灌喂碳酸锂15 mg.d-15 d后,于d 6开始灌喂丙戊酸钠10 mg.d-1,2种药物共同灌喂3 wk;对照组仅喂碳酸锂15 mg.d-1。分别于d 5、12、19、26抽取尾血2 mL,用于测定碳酸锂血清水平。结果2组4次的碳酸锂血清水平分别是:研究组,(0.198±0.051)(、0.215±0.062)(、0.137±0.042)(、0.177±0.122)mmol.L-1,F=1.949,P=0.139;组内差异无显著性。对照组,(0.172±0.057)(、0.185±0.054)(、0.186±0.059)(、0.180±0.029)mmol.L-1,F=0.166,P=0.919;组内差异无显著性。研究组与对照组血清锂水平比较,仅第3次差异有统计学意义(P<0.05)。结论动物实验表明,丙戊酸钠对碳酸锂的血清水平几乎没有影响,不会引起碳酸锂水平的增高。     

High sodium intake increases the urinary excretion of L-3,4-dihydroxyphenylalanine but fails to alter the urinary excretion of dopamine and amine metabolites in wistar rats

• 1.1. The present study has examined the daily urinary excretion of L-DOPA, dopamine and its metabolites (DOPAC, 3-MT and HVA) during normal salt (NS) and high salt (HS) diets.
• 2.2. Daily urinary excretion of L-DOPA, DA, DOPAC, 3-MT and HVA during the 4-day period of NS diet averaged, respectively, 7.6±0.4, 71±5,217±22, 570±90and1217±110 nmol/kg/day. The slight increase in the urinary excretion of DA, DOPAC and 3-MT (16% to 42% increase), when rats were fed a HS diet, did not achieve statistical significance.
• 3.3. In contrast, the urinary levels of L-DOPA during the HS diet period (11 ± 1 nmol/kg/day) were found to be significantly higher than during the NS diet period; the maximal increase in the urinary excretion of L-DOPA (93% increase) was observed in the first day and then a progressive decline was observed towards the end of the HS intake period.
• 4.4. During the first 5 days of the HS intake period, the urine output of noradrenaline (NA) was found to increase (27% to 83%) and then to progressively decline to baseline values (13.5±0.7 nmol/kg/day).
• 5.5. Urinary excretion of adrenaline (AD) during the HS intake period was found to increase (72% to 146%); the mean daily urinary excretion of AD during the NS diet period averaged 2.5±0.4 nmol/kg/day. NA and DA contents in the kidney of rats on a NS diet were not significantly different from that of rats in a HS diet.
• 6.6. It is concluded that long-term HS intake in Wistar rats fails to change the urinary excretion of DA and of its metabolites (DOPAC, 3-MT and HVA). Furthermore, the discrepant profile in the urinary excretion of L-DOPA and DA during HS intake might be related to a reduction in the tubular uptake of the amino acid, rather than reflecting a decrease in its decarboxylation.

     

Blood-to-muscle distribution and urinary excretion of higenamine in rats

Higenamine is a β₂-agonist that has been prohibited in sports by the World Anti-Doping Agency. Higenamine could potentially promote anabolism and lipolysis; however, its crucial pharmacokinetics data, particularly muscle distribution, remain unavailable. The present study aims to investigate the blood-to-muscle distribution as well as the urinary excretion of higenamine in laboratory rats. In the first experiment, the microdialysis technique was employed to continuously measure free, protein-unbound concentrations in blood and muscle for 90 min (sampling at a 5-min interval) after rats received IV infusion of higenamine. The mean half-lives of higenamine in blood and muscle were 17.9 and 19.0 min, respectively. The blood-to-muscle distribution ratio (AUC_muscle/AUC_blood) of higenamine was estimated to be 22%. In the second experiment, rats were orally administered with a single-dose higenamine, and their urine samples were profiled at a 12-h interval for up to 48 h. Results showed only a small portion of total consumption (1.44%, ranging 0.71%–2.50%) was excreted in the urine. Among these time points, about 43% cumulative amount of higenamine was eliminated within the first 12 h. Our data suggested that one-quarter of the unbound higenamine rapidly penetrates from the vessels into muscle, distributes to the interstitial fluid, then eliminates from the rat in a short span of time. The muscle tissue is likely to have a low binding affinity for higenamine, and renal excretion plays a minor role in its elimination. Together, our findings provide valuable pharmacokinetics data that may gain deeper insights into higenamine's role in skeletal muscle functions.     

The effects of sodium chromate and carbon tetrachloride on the urinary excretion and tissue distribution of cadmium in cadmium-pretreated rats

Rats were administered nontoxic doses of Cd²⁺ by the oral or intraperitoneal routes. They were subsequently treated with either Na₂CrO₄ (10 or 20 mg/kg, sc) or CCl₄ (0.5 or 1 ml/kg, intragastric). Evidence of renal damage was obtained from the determination in urine of total protein and amino acids and from the analysis of the urinary proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liver damage was evaluated by determining the serum activities of sorbitol dehydrogenase and glutamate pyruvate transaminase. The effects of CCl₄ on the urinary excretion and the tissue distribution of Cd²⁺ vary depending on whether liver damage is associated or not with extensive renal lesions. When renal function was not or only moderately altered, induction of liver damage by CCl₄ resulted in a transfer of Cd²⁺ from the liver to the kidney. This transfer was evidenced by a decrease of total Cd²⁺ as well as metallothionein-bound Cd²⁺ in the liver and an increase of the same parameters in the kidney. The urinary excretion of Cd²⁺ was only slightly increased. When liver damage induced by CCl₄ was associated with extensive kidney lesions, the accumulation of Cd²⁺ released from the liver in the kidney was considerably reduced and large amounts of Cd²⁺ were excreted in urine. Administration of Na₂CrO₄ to Cd²⁺-pretreated rats gave rise to a sharp and reversible increase in the urinary excretion of Cd²⁺. This increase was proportional to the amount of Cd²⁺ stored in kidney and to the dose of Na₂CrO₄ administered. The Cd²⁺ excreted in urine originated mainly from the kidney in which total Cd²⁺ and metallothionein-bound Cd²⁺ were reduced in proportion to the dose of Na₂CrO₄ administered. These results suggest that two mechanisms may lead to an increased urinary excretion of Cd²⁺; a direct release of Cd²⁺ into urine from damaged kidney (i.e., Na₂CrO₄) or a decreased tubular reabsorption of plasma circulating Cd²⁺ evidenced when large amounts of Cd²⁺ are released into blood from damaged liver (i.e., CCl₄). These results tend to support the hypothesis that kidney damage due to chronic Cd²⁺ poisoning may lead to an increased loss of the Cd²⁺ stored in the kidney.     

A role of renal K+-stimulated phosphatase activity on elevation of urinary sodium excretion in fluoride-treated rats

Fluoride administered to nonfasted rats caused an elevation of urinary sodium excretion but not an increased urinary potassium excretion as previously observed by one of us in fasted rats. This elevated urinary sodium excretion was associated with decreased renal K+-stimulated phosphatase activity. The decreased phosphatase activity was reversed by treatment with aldosterone, but not by treatment with prednisolone.     

Pharmacokinetics and urinary excretion of eprosartan in Chinese healthy volunteers of different gender

The study aims to evaluate the pharmacokinetics and urinary excretion of eprosartan in Chinese healthy volunteers and to study the effect of gender on pharmacokinetics of eprosartan. Twenty healthy volunteers (ten men and ten women) were recruited for an open trial and received a single dose of 600 mg eprosartan. Using a validated LC/MS/MS method, plasma and urinary concentrations of eprosartan were determined. The following pharmacokinetic parameters were elucidated after administration: the area under the plasma concentration versus time curve from 0 to 32 h (AUC0-32h) 14818.75 +/- 7312.11 ng x h/mL, the area under the plasma concentration versus time curve from 0 to infinite (AUC(0-infinity)) 15081.62 +/- 7379.63 ng x h/mL, peak plasma concentration (Cmax) 3664.25 x 1653.94 ng x h/mL, time to Cmax (Tmax) 1.63 +/- 0.46 h, elimination half-life (t(1/2)) 8.03 +/- 4.04 h, apparent clearance (CL/F) 47.84 +/- 19.21 L/h, apparent volume of distribution of the central compartment (V/F) 537.21 +/- 287.91 L, renal clearance (CLr) 1.33 +/- 0.41 L/h, amount of unchanged eprosartan excreted into urine 18.44 +/- 6.43 mg and fraction of unchanged eprosartan excreted into urine 3.07 +/- 1.07%. Our results also indicated that no gender differences were observed in the pharmacokinetics of eprosartan in Chinese healthy volunteers.     

高效毛细管气相色谱法测定片剂中丙戊酸钠含量

目的:建立高效毛细管气相色谱法测定丙戊酸钠片剂的含量.方法:用水溶解丙戊酸钠,加盐酸使其转化为丙戊酸,用乙醚萃取净化样品.色谱柱为AT SE-54高效毛细管色谱柱(15 m×0.25 mm,0.33μm).柱前压:0.015 MPa;进样口温度:215℃;检测器:FID;温度:215℃;载气为N2,流速:18mL·min-1;空气150 mL·min-1;氢气62 mL·min-1;Makeup(氮气)10 mL·min-1.结果:丙戊酸在2～20 g·L-1浓度范围内线性关系良好(r=0.999 8),丙戊酸高、中、低(16.0,8.0,4.0 g·L-1)回收率分别为100.3%,99.0%,98.8%.结论:本法简便、快速、准确,可用于丙戊酸钠片的含量测定.