Pharmacokinetics of tranexamic acid after intravenous, intramuscular, and oral routes: a prospective, randomised, crossover trial in healthy volunteers

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic TechnologyTM (Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729). In a two-step hypothesis, the primary endpoints were (i) significant reduction in peak plasma concentrations (Cmax) of essential amino acids (EAAs) while (ii) maintaining EAA bioavailability (AUC0-300 min) compared to a free AA mixture (Reference). Secondary endpoints included effects on plasma profiles of other AA groups and effects on several metabolic markers. Thirty subjects completed the study. Both co-primary endpoints were met: Cmax for EAAs was 27% lower with the Test product compared to the Reference product (ratio, 0.726, p < 0.0001); overall plasma EAA levels from the two AA mixtures was within the pre-specified bioequivalence range (AUC0-300min ratio, 0.890 (95% CI: 0.865, 0.915)). These findings were supported by the results of secondary endpoints. Prolongation of AA absorption was associated with modulation of several metabolic markers. It will be important to understand whether this can improve the long-term management of disorders of AA metabolism.

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Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males

British Journal Of Nutrition ◽

10.1017/s0007114507803953 ◽

2008 ◽

Vol 99 (2) ◽

pp. 333-344 ◽

Cited By ~ 25

Author(s):

Sébastien Vergne ◽

Catherine Bennetau-Pelissero ◽

Valérie Lamothe ◽

Philippe Chantre ◽

Mylène Potier ◽

...

Keyword(s):

Healthy Volunteers ◽

Crossover Trial ◽

Human Subjects ◽

Biologically Active ◽

Pharmacokinetic Parameters ◽

Relative Importance ◽

Elisa Method ◽

Isoflavone Content ◽

Derivative Products ◽

Healthy Males

Soya isoflavones, genistein and daidzein, are the focus of numerous studies investigating their potential effects on health and results remain controversial. Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies. This study aimed at assessing: (1) the isoflavone content of sixty-nine European soya-derivative products sold on the French market; (2) the bioavailability of isoflavones comparing supplement with food. Twelve healthy volunteers were recruited in a randomized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese, both containing different patterns of isoflavone conjugates and different daidzein:genistein ratios. A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters, which were then normalized to mg of each isoflavone ingested. Results showed that the normalized Cmax of daidzein (P = 0·002) and similarly the normalized AUC0 → ∞andCmaxof genistein (P = 0·002) from soya-based capsules were higher than that from soya-based cheese. In conclusion, this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products. Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability, this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese. Although the supplement is more bioavailable, the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy.

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Inhibition of Platelet Aggregation in Man by Indobufen (K 3920)

Journal of International Medical Research ◽

10.1177/030006058100900103 ◽

1981 ◽

Vol 9 (1) ◽

pp. 12-17 ◽

Cited By ~ 6

Author(s):

A Vittoria ◽

F Laghi Pasini ◽

G L Messa ◽

T Di Perri ◽

G Corvi ◽

...

Keyword(s):

Platelet Aggregation ◽

Healthy Volunteers ◽

Crossover Trial ◽

Marked Effect ◽

Threshold Concentration ◽

Dose Effect ◽

Inhibition Of Platelet Aggregation ◽

Oral Doses

A complete crossover trial was undertaken in six healthy volunteers to gain information on dose-effect responses to indobufen by assessing the intensity and duration of the effect of 3 single oral doses of the drug on platelet aggregation induced by threshold concentration of ADP and by 3 added doses of collagen. The results of the study confirm that the activity is dose-related and is reversible since 24 hours after administration it has practically disappeared. The effect of the same dose of indobufen differed significantly according to the amount of collagen added to plasma, whereas increasing doses of indobufen provoked a significantly more marked effect when the amount of inducer employed was the same.

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Comparative study of electronic vs. paper VAS ratings: a randomized, crossover trial using healthy volunteers

Pain ◽

10.1016/s0304-3959(02)00178-1 ◽

2002 ◽

Vol 99 (1) ◽

pp. 341-347 ◽

Cited By ~ 124

Author(s):

Robert N. Jamison ◽

Richard H. Gracely ◽

Stephen A. Raymond ◽

Jonathan G. Levine ◽

Barbara Marino ◽

...

Keyword(s):

Comparative Study ◽

Healthy Volunteers ◽

Crossover Trial ◽

Randomized Crossover Trial

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Effects of Single Oral Doses of Gemifloxacin (320 Milligrams) versus Trovafloxacin (200 Milligrams) on Fecal Flora in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.2.608-611.2001 ◽

2001 ◽

Vol 45 (2) ◽

pp. 608-611 ◽

Cited By ~ 9

Author(s):

Gloria Garcia-Calvo ◽

Ana Molleja ◽

Maria J. Giménez ◽

Araceli Parra ◽

Eva Nieto ◽

...

Keyword(s):

Escherichia Coli ◽

Healthy Volunteers ◽

Washout Period ◽

Crossover Trial ◽

Fecal Flora ◽

Randomized Crossover Trial ◽

The Family ◽

Stool Samples ◽

Resistant Strains ◽

Oral Doses

ABSTRACT Gemifloxacin and trovafloxacin were administered to 12 volunteers in a randomized crossover trial with a 2-week washout period. Stool samples were collected predose and 1, 2, and 3 days postdose. Both quinolones reduced the number of organisms of the familyEnterobacteriaceae and aerobic gram-positive organisms. Escherichia coli reduction was greater with gemifloxacin than with trovafloxacin, with postdose isolation of quinolone-resistant strains for which MICs of trovafloxacin were higher than those of gemifloxacin.

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