Urinary Elimination of Ecdysterone and Its Metabolites Following a Single-Dose Administration in Humans

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting, and anabolic effects, mediated by the activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program, to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urine samples in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid-chromatography–tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy-ecdysterone and 14-deoxy-poststerone, was achieved. Ecdysterone was the most abundant analyte present in post-administration urine samples, detected for more than 2 days, with a maximum concentration (Cmax) in the 2.8–8.5 h urine (Cmax = 4.4–30.0 µg/mL). The metabolites 14-deoxy-ecdysterone and 14-deoxy-poststerone were detected later, reaching the maximum concentrations at 8.5–39.5 h (Cmax = 0.1–6.0 µg/mL) and 23.3–41.3 h (Cmax = 0.1–1.5 µg/mL), respectively. Sex-specific differences were not observed. Cumulative urinary excretion yielded average values of 18%, 2.3%, and 1.5% for ecdysterone, 14-deoxy-ecdysterone, and 14-deoxy-poststerone, respectively. Ecdysterone and 14-deoxy-ecdysterone were excreted following first-order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy-poststerone needs further evaluation.

Urinary Elimination of Ecdysterone and its Metabolites following a Single-Dose Administration in Humans

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting and anabolic effects mediated by activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urines in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid chromatography-tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy ecdysterone and 14-deoxy poststerone was achieved. Ecdysterone was the most abundant analyte present in post-administration urines, detected for more than 2 days with a maximum concentration (Cmax) in the 2.8-8.5 h urines (Cmax = 4.4-30.0 µg/mL). The metabolites 14-deoxy ecdysterone and 14-deoxy poststerone were detected later reaching the maximum concentrations at 8.5-39.5 h (Cmax = 0.1-6.0 µg/mL) and 23.3-41.3 h (Cmax = 0.1-1.5 µg/mL), respectively. Cumulative urinary excretion yielded average values of 18%, 2.3% and 1.5% for ecdysterone, 14-deoxy ecdysterone and 14-deoxy poststerone, respectively. Ecdysterone and 14-deoxy ecdysterone were excreted following first order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy poststerone needs further evaluation.

Pharmacokinetics of CS-023 (RO4908463), a Novel Parenteral Carbapenem, in Healthy Male Caucasian Volunteers

ABSTRACT The CS-023 concentration in plasma after administration by infusion to healthy volunteers at a dose of 700 mg was decreased, with a half-life of 1.7 h, and the cumulative urinary excretion was 59.4% of the dose. The total clearance, renal clearance, and volume of distribution were 8.12 liters/h, 4.14 liters/h, and 17.2 liters, respectively.

Gastrointestinal absorption, tissue retention, and urinary excretion of dietary aluminum in rats determined by using 26Al

We used accelerator mass spectrometry (AMS) and 26Al to study the plasma concentration, urinary excretion, and retention in bone, brain, and liver of a single dose of a dietary concentration of aluminum ingested either with or without citrate by 2-month-old Wistar rats. In the absence of citrate, cumulative urinary excretion and skeleton retention were each ∼0.05% of the total 26Al dose ingested. 26Al retention in brain and liver were ∼4 × 10−8 and 2 × 10−6, respectively. Concomitant citrate intake increased these median values by about two- to fivefold, although this factor was highly variable in individual rats. Independent of citrate administration, 90% of the26Al excreted in urine (measured cumulatively over 30 days) was excreted within the first 48 h. Uptake by bone was rapid (∼1 h) and permanent over the 30-day duration of the experiment.

Absorption of Digoxin from Tablets and Capsules in Subjects with Malabsorption Syndromes

The relative steady-state bioavailability of two oral digoxin dosage forms was studied in 17 subjects with malabsorption syndromes. Male subjects received the following treatments in randomized crossover fashion for 14 days: Three 0.125-mg digoxin tablets or three 0.1-mg digoxin capsules once daily. Female subjects received digoxin on the same schedule but at two-thirds the dose. Serum and urine samples were collected and analyzed for digoxin by radioimmunoassay, and treatments were compared by evaluating pharmacokinetic parameters. The mean area under the serum concentration versus time curve for tablets (28.1 h•nmol/L [21.9 h•ng/mL]) was smaller (p < 0.03) than that for capsules (31.1 h•nmol/L [24.3 h•ng/mL]), and the mean maximum serum digoxin concentration for tablets (2.9 nmol/L [2.3 ng/mL]) was lower (p < 0.02) than that for capsules (4.0 nmol/L [3.1 ng/mL]). There was no difference in cumulative urinary excretion of digoxin between the two treatments. In contrast to previous reports, we observed that digoxin from Lanoxin Tablets appears to be well absorbed in subjects with malabsorption. Nevertheless, these subjects absorbed digoxin from capsules better than from tablets, with the greatest differences occurring in subjects without a colon and in those subjects with the lowest serum carotene concentrations.

Pharmacokinetics and metabolism of epidoxorubicin and doxorubicin in humans.

Pharmacokinetics of doxorubicin (DOX), epidoxorubicin (EPI), and their metabolites in plasma have been performed in eight patients receiving 40 to 56 mg/m2 of both anthracyclines as a bolus injection in two sequential cycles. Terminal half-life and volume of distribution appeared to be smaller in case of EPI, whereas plasma clearance and cumulative urinary excretion was larger in comparison to DOX. The major metabolite of DOX was doxorubicinol (Aol) followed by 7-deoxy-doxorubicinol (7d-Aolon). Metabolism to glucuronides was found in case of EPI only. The area under the curves (AUC) of the metabolites of EPI decreased in the order of the glucoronides E-glu greater than Eol-glu, 7d-Aolon greater than epirubicinol (Eol). The AUC of Eol was half of the value in its counterpart Aol. In the case of EPI, the AUC of 7d-Aolon was twice the level of that of the corresponding metabolite of DOX. The terminal half-lives of the cytostatic metabolites Aol and Eol were similar, but longer than the corresponding values of their parent drugs. Half-lives of the glucuronides (E-glu, Eol-glu) were similar to the half-life of their parent drug. 7d-Aolon had a somewhat shorter half-life in comparison to both DOX and EPI. Approximately 6.2% of EPI and 5.9% of DOX were excreted by the kidney during the initial 48 hours. Aol was found in the urine of patients treated with DOX, whereas Eol, E-glu, and Eol-glu were detected in urine of patients treated with EPI. The cumulative urinary excretion appeared to be 10.5% for EPI and its metabolites, and 6.9% for DOX and its metabolite. The plasma concentration v time curves of (7d)-aglycones showed a second peak between two and 12 hours after injection, suggesting an enterohepatic circulation for metabolites lacking the daunosamine sugar moiety. The plasma concentrations of the glucuronides were maximal at 1.2 hours for E-glu and 1.9 hours for Eol-glu. All other compounds reached their maximum plasma concentration during the first minutes after the administration of DOX and EPI. Deviating plasma kinetics were observed in one patient, probably due to prior drug administration.

The Metabolism of Ceramic and Non-ceramic Forms of Uranium Dioxide after Deposition in the Rat Lung

Ceramic and non-ceramic forms of uranium dixoide, produced industrially, were administered to rats either by inhalation or as an aqueous suspension which was injected directly into the pulmonary region of the lungs. The results showed that: 1 both materials should be assigned to inhalation class Y as defined by the International Commission on Radiological Protection; 2 whilst the translocation of uranium to the blood for the non-ceramic UO2 was about twice that obtained for the ceramic form, the two dioxides were unlikely to be differentiated on the basis of their lung retention kinetics; 3 the distribution of uranium amongst body tissues and the relationship between systemic content and cumulative urinary excretion indicated that it was transported in the hexavalent form; 4 in addition to air sampling procedures, lung radioactivity counting measurements could be used to advantage for assessing occupational exposures; 5 the exposure limits should be based on radiation dose rather than chemical toxicity.

Effect of Purgatives on Antidotal Efficacy of Oral Activated Charcoal

1 The effects of purgatives on the antidotal efficacy of oral activated charcoal were studied in seven volunteer subjects. 2 The volunteer subjects were given 1000 mg of aspirin, 100 mg of atenolol and 50 mg of phenylpropanolamine with 100 ml of water on an empty stomach and were assigned randomly to the following treatment groups: (A) after 5 min 150 ml of water, (B) after 5 min 25 g of charcoal, (C) after 5 min charcoal orally with 20 mg of metoclopramide rectally, followed by 10 mg of bisacodyl rectally 3 h afterwards, (D) after 5 min charcoal with 250 ml of magnesium citrate USP and (E) after 60 min charcoal with metoclopramide followed by bisacodyl 3 h thereafter. 3 The plasma concentrations (0-24 h) and the cumulative urinary excretion (0-72 h) of salicylates, atenolol and phenylpropanolamine were measured. 4 Both magnesium citrate and metoclopramide combined with bisacodyl hastened the gastrointestinal transit but magnesium citrate was more effective. 5 Charcoal alone reduced the absorption of aspirin and phenylpropanolamine by about 50% and that of atenolol by about 95%. The purgatives did not modify significantly the efficacy of charcoal. 6 When the antidotal treatment was delayed by 60 min its efficacy was reduced to some extent, possibly depending on the pharmaceutical formulation of the test drugs. 7 The present results do not support the routine use of purgatives in combination with activated charcoal. In some instances, however, their use may promote the evacuation of, for example, depot formulations from the gastrointestinal tract and thus have a beneficial effect together with activated charcoal in reducing absorption.