Plasma pyroglutamic acid levels after oral administration of monosodium glutamate to human volunteers

Plasma levels of pyroglutamic (PY) and glutamic (GA) acids have been measured after oral administration of monosodium glutamate (MSG) to 6 human volunteers. MSG (43 mg/kg) was administered either after an overnight fast or immediately after a normal meal. In fasting subjects plasma GA peak levels were about 2.3 times the basal levels whereas the increase in plasma PY levels were only 1.5-fold. When MSG was administered with a meal plasma GA levels were raised, to a lesser extent, while no increase could be observed in plasma PY.     

Pharmacokinetics of cefatrizine after oral administration in human volunteers

The oral bioavailability of cefatrizine was studied in four groups, each of ten healthy young male volunteers. Capsules and suspension formulations were each administered at doses of 250 and 500 mg. Both the capsules and suspensions had mean peak plasma levels at 1.6 h at both dose levels. Mean peak plasma levels were 4.1 and 4.3 micrograms/ml for the 250 mg capsule and suspension doses respectively and 7.1 and 7.5 micrograms/ml for the 500 mg capsules and suspension doses respectively. The overall mean half-life was 1.7 h. For both types of formulations and at both dose levels 63-65% of the doses were excreted in the urine as intact cefatrizine, 85% of this amount within 8 h. The overall mean renal clearance was 157 ml/min. The cefatrizine capsule and suspension formulations were completely bioequivalent in regard to both rate and extent of bioavailability. Plasma concentrations and urinary recoveries of cefatrizine were higher than those previously reported, due to precautions taken in sample collection and storage.     

Naproxen plasma levels in volunteers after single-dose administration by oral and rectal routes.

The bioavailability (plasma concentrations, AUC) of a rectal formulation (suppository) of naproxen was investigated in six healthy volunteers by comparison with an oral preparation (tablets). Plasma half-lives after both formulations were identical 10 hr 15 min+/-25 min (S.D.). Determined by the AUC the bioavailability of naproxen in the suppositories was 94.8%+/-6.3% of the bioavailability of naproxen in the tablets. This paper describes also a new gas-liquid chromatographic method for determining unchanged naproxen in human plasma which is quick, sensitive, and specific.     

Pharmacokinetics of huperzine A following oral administration to human volunteers.

The objective of the present study was to investigate the in vivo pharmacokinetics of huperzine A in healthy human volunteers. Twelve subjects (M 6, F 6; age ranged from 20-25 years) participated in the study. Huperzine A was administered in tablet form at a single dose of 0.4 mg. Following oral administration, the presence of huperzine A started to appear in the plasma at 5-10 min, and reached the peak concentrations with a Cmax of 2.59 +/- 0.37 ng/ml at 58.33 +/- 3.89 min (time to reach peak level, Tmax. The area under plasma vs time curve (AUC(0-t)) and the area under plasma from zero to infinity (AUC(0-infinity) for huperzine A were found to be 1986.96 +/- 164.57 microg/l.min and 2450.34 +/- 233.32 microg/l.min, respectively. The results of this study indicated that the pharmacokinetics of huperzine A conformed to a two-compartmental open model. The mean values of alpha and the beta half-life were 21.13 +/- 7.28 min and 716.25 +/- 130.18 min respectively, and showed a biphasic profile with rapid distribution followed by a slower elimination rate.     

Effects and plasma levels of N-desmethyldiazepam after oral administration in normal volunteers

In the course of a previous study on the pharmacokinetics and effects of diazepam in anxiety patients, it was hypothesized that the N-desmethyl derivative is a disturbing agent causing side effects. The present study served to test the validity of this assumption.Diazepam and N-desmethyl-diazepam, the latter as a separate drug, were orally administered to 6 subjects, each drug during 7 days, 15 mg daily in divided doses.Using a randomized, placebo controlled, double-blind design, subjective and observer ratings of a wide range of clinical effects were made. Plasma levels of the benzodiazepine compounds were determined by the G.L.C. method. Results showed that steady state plasma levels were reached on the 5th day; that N-desmethyldiazepam, considering its lower clearance rates, is a longer acting drug than diazepam; that both substances induce hypnosedative effects, mood changes, and somatic disturbances and facilitate sexual behaviour in normals; that desmethyldiazepam is a more effective hypnosedative and mood-lowering substance as compared to equal doses of diazepam. Further comparisons in anxiety patients are recommended in order to find out if the specific desmethyldiazepam effects are therapeutically favourable or disturbing.     

Effect of combined administration of clofibrate and neomycin on serum cholesterol levels in familial type II hyperlipoproteinaemia

Summary

Eight patients suffering from familial Type II hyperlipoproteinaemia were treated with clofibrate for a period of 12 weeks and this was followed by combined therapy with clofibrate and neomycin for a further period of 12 weeks. It was found that neomycin, though free from major side-effects, failed to augment the hypocholesterolaemic action of clofibrate.     

Effect of continuous silymarin administration on oral talinolol pharmacokinetics in healthy volunteers

1. The objective of this study was to investigate the effect of concomitantly administered silymarin on the pharmacokinetics of talinolol, a typical substrate for P-glycoprotein (P-gp), in healthy Chinese volunteers and its association with a multidrug resistance 1 (MDR1) C3435T genetic polymorphism.

2. Eighteen healthy adult men (six MDR1 3435CC homozygotes, six MDR1 3435CT heterozygotes and six MDR1 3435TT homozygotes) were recruited in a two-phase, randomized, single-blind, crossover design. The pharmacokinetics of talinolol were measured after co-administration of placebo or 140?mg silymarin capsules three times daily for 14 days. Concentrations of talinolol in plasma were measured for up to 36?h after drug administration by liquid chromatography-mass spectrometry (HPLC-MS).

3. The peak plasma concentration (C_max) of talinolol was significantly higher after silymarin administration as compared with placebo (p?=?0.007). The area under the plasma concentration–time curve from zero to 36?h (AUC_0–36) and AUC_0–∞ of talinolol was increased by 36.2% ± 33.2% and 36.5% ± 37.9%, respectively, by silymarin co-administration. The oral clearance (CL/F) of talinolol was decreased by 23.1% ± 16.6% (p?t_max) and the blood elimination half-life (t_1/2) of talinolol was observed between the placebo- and silymarin-treated phases.

4. Co-administration of silymarin significantly increased the plasma concentration of talinolol in healthy volunteers.

     

Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin.

Effect of oral administration of curcumin (diferuloyl methane) on lipid peroxidation in various organs of mice like liver, lung, kidney and brain was studied in control animals as well as those given carbon tetrachloride, paraquat and cyclophosphamide. Oral administration of curcumin significantly lowered the increased peroxidation of lipids in these tissues produced by these chemicals. Administration of curcumin was also found to lower significantly the serum and tissue cholesterol levels in these animals, indicating that the use of curcumin helps in conditions associated with peroxide induced injury such as liver damage and arterial diseases.     

Pharmacokinetics of pramiracetam in healthy volunteers after oral administration.

The pharmacokinetics of pramiracetam was assessed using an HPLC method after oral administration of two different formulations of 600 mg (a solution and a tablet) of pramiracetam to 11 fasting volunteers. The mean kinetic parameters were: t1 = 4.7 +/- 2.4 - 4.3 +/- 2.2 h, AUC = 57.6 +/- 43.6 - 47.2 +/- 33.9 micrograms h/ml, Cmax = 6.80 +/- 3.2 - 5.80 +/- 3.3 micrograms/ml for the solution and the tablet respectively. The plasma profile of pramiracetam proved to be not highly affected by the formulation, only that the absorption rate was faster after oral administration of the drug in solution than after administration as a tablet. The half-life was very variable between subjects [2-8 hours], but less variable within subjects and it was unaffected by the formulation.     

姜黄素口服吸收制剂的研究进展

姜黄素具有多种生物活性,但由于其水溶性差,在肠道吸收过程中易发生生物转化,口服生物利用度低,在临床应用中受到极大限制.利用现代制剂技术促进其口服吸收,已成为研究的热点,本文根据近年来发表的相关文献,对姜黄素口服吸收制剂的研究情况进行了介绍.     

Effect of intermittent administration of omeprazole on serum pepsinogens in duodenal ulcer patients and healthy volunteers.

1. Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K(+)-APT-ase, was administered orally at a dose of 20 mg in the morning of 3 consecutive days, followed by a period of 4 days without medication, and this intermittent dosage regimen was continued for 4 weeks. 2. During intermittent administration of omeprazole to 10 patients with duodenal ulcer disease and 10 healthy volunteers concentrations of serum pepsinogen A and serum pepsinogen C were monitored by sensitive and specific radioimmunoassays to study whether the effect of this treatment on serum pepsinogens is different between patients and normal subjects and to evaluate whether serum pepsinogen levels can be used to assess compliance with therapy. 3. Administration of omeprazole for 3 days induced significant increases in pepsinogen A and pepsinogen C serum concentrations, which rapidly fell after stopping the omeprazole intake. The pattern of serum pepsinogens after stopping the drug was different for duodenal ulcer patients and normal subjects. Both pepsinogens were intra-individually related in both patients and healthy subjects when compared during the first and last 3-day course with omeprazole, but in duodenal ulcer patients both pepsinogens tended to be higher in the last treatment course, while the opposite was found in the normal subjects. 4. The present study confirms that serum pepsinogen concentrations are higher in duodenal ulcer patients than in normal subjects, but also shows for the first time that serum pepsinogens in the patients respond differently upon stimulation with omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous and oral administration.

The concentration-time profiles of metabolites of moxisylyte, an alpha-blocking agent, in the plasma and urine of 12 healthy volunteers were investigated after intravenous (iv) and oral (two formulations) administration. The study was conducted with an open, randomized Latin squares design. Plasma and urine levels of moxisylyte and its biotransformation products were assayed by a specific HPLC method with fluorescence detection. Plasma levels declined in a monophasic or biphasic pattern depending on the subject. Two metabolites, conjugated desacetylmoxisylyte (DAM) and conjugated monodesmethylated DAM (MDAM), were found in plasma and urine. Unconjugated DAM was found in plasma only after iv administration. The apparent elimination half-lives of unconjugated DAM, conjugated DAM, and MDAM were 0.86, 1.7, and 3 h, respectively. The total amounts of metabolites (expressed as the equivalent of DAM) excreted in the urine were 75% after i.v. administration and 68 and 69% after oral administration of the two formulations. Oral absorption appeared to be complete for the two treatments. There was no statistical difference between the two oral formulations studied.     

The impact of high-dose statin therapy on transendothelial neutrophil migration and serum cholesterol levels in healthy male volunteers

Rationale  

Cardiac surgery presents a risk to all major organs due to activation of the systemic inflammatory response. Patients referred for cardiac surgery are typically older, usually have comorbid conditions, and are thus at higher risk of postoperative multiorgan dysfunction. Patients demonstrating evidence of organ dysfunction require intensive postoperative management. Any means to predict and reduce the inflammatory response mounted postcardiac surgery could translate into a clinical benefit for the patient and reduce the length of stay in intensive care.     

Preliminary study on the absorption profile after rectal and oral administration of methadone in human volunteers

Methadone is a potent, long acting narcotic analgesic which can be orally administered due to its almost complete bioavailability. There is a growing interest in the rectal route of administration in the case of acute postoperative or chronic malignant pain. Since virtually no data were available on the rectal absorption profile of methadone in man, plasma concentrations of methadone were determined by means of HPLC analysis after a single dose of 10 mg methadone HCl in a cross-over pilot study in five volunteers. The rectal dosage forms included aqueous solutions and fatty suppositories. A comparison was made with an orally administered solution. Compared with oral dosing, the extent of rectal absorption from an aqueous solution was almost 80% up to 8 h after dosing. Although the mean peak concentration and the AUC_0-8h was significantly lower (p < 0.01), no marked difference in t_max was observed: 2.8 and 3.1 h respectively. Rectal absorption conditions of methadone from fatty suppositories (3 ml) were found to be less favourable. The peak plasma concentration was only reached 3–4 h after administration, whereas the relative bioavailability up to 8 h after dosing ranged from 35–58%. This rate-limiting absorption pattern may be due to the critical solubility properties of methadone HCl at physiological pH.     

Pharmacokinetics of benperidol in volunteers after oral administration

Benperidol in a 4 mg single dose was administered orally to five healthy male volunteers. The drug was rapidly absorbed (tmax = 2.27 +/- 0.57 h) and largely distributed, the volume of distribution being 5.19 +/- 1.99 l.kg-1. Elimination half-life was 7.65 +/- 2.14 h. Urinary excretion represented only a minimal fraction of ingested dose (0.1 +/- 0.007%). Variability of the area under the curve makes a first-pass metabolism a reasonable possibility. Acute dystonias appeared in two subjects.     

Effect of prolonged trifluoperazine, imipramine and haloperidol administration on serum cholesterol. An experimental study in rabbits.

As a result of prolonged intragastric administration of trifluoperazine (TFZ) and imipramine in rabbits, a significant rise in serum cholesterol was observed after 4, 8 and 12 weeks. Haloperidol was ineffective. Hypercholesterolemia produced by TFZ was not associated with increased estriol excretion in urine. Histochemical examination of aorta of TFZ-treated animals showed positive 'Schultz's reaction' for cholesterol, suggesting a possible causal relationship between TFZ-induced hypercholesterolemia and atherogenesis.     

法莫替丁对多潘立酮在健康人体药代动力学的影响

目的观察法莫替丁对多潘立酮药代动力学的影响。方法随机分组,10名健康志愿者未服和服用法莫替丁后单剂量口服多潘立酮10mg,用LC/MS/MS测定血药浓度,DAS软件计算药代动力学参数,t检验、非参数检验比较主要药代动力学参数。结果未服和服用法莫替丁后单剂量口服多潘立酮的血药浓度时间曲线均符合二室模型,达峰时间tmax分别为0.63±0.36、1.50±0.97h,峰浓度Cmax分别为9.91±5.45、4.30±5.01μg·L-1,曲线下面积AUC0-tn分别为39.57±10.46、32.43±9.61μg·h·L-1。服用法莫替丁后,多潘立酮的达峰时间延长,血药浓度时间曲线下面积减少,峰浓度降低,且均有统计学意义。结论在健康人体内,法莫替丁对多潘立酮的药代动力学参数影响显著。     

Controlled systemic delivery by polymeric implants enhances tissue and plasma curcumin levels compared with oral administration

Curcumin possesses potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ～2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ～3.3 ng/ml on day 1, which dropped to ～0.2 ng/ml after 3 months, whereas only 0.2-0.3 ng/ml concentration was observed from 4-12 days with diet and was undetected subsequently. Almost 10-fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1 ± 7.3 vs 2.7 ± 0.8 ng/g) and were still significant even after 90 days (7.7 ± 3.8 vs 2.2 ± 0.8 ng/g). Although curcumin levels were similar in liver from both the routes (～25-30 ng/g from day 1-4 and ～10-15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ～28-fold lower doses at 90 days. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain.