The comparability of etanercept pharmacokinetics in healthy Japanese and American subjects.

Thirty Japanese (J) and 32 American (A) healthy subjects received single doses of etanercept by subcutaneous injection, in 3 separate trials. Serum samples were collected for 480 hours after dosing. Concentrations were determined using enzyme-linked immunosorbent assay methods. Pharmacokinetic parameters were calculated using both non-compartmental and compartmental methods. Etanercept was slowly absorbed, with mean+/-SD time to maximum serum concentration of 47+/-15 hours (J), and 51+/-20 hours (A). The maximum serum concentration and area under the concentration time curve increased for doses 10 mg, 25 mg, and 50 mg, in a linear relationship. Etanercept was slowly eliminated, with observed mean+/-SD half-life of 80+/-25 hours (J) and 75+/-15 hours (A) and mean+/-SD apparent clearance of 144+/-65 mL/h (J) and 132+/-74 mL/h (A). Very low concentrations of etanercept were observed in the urine samples collected in the Japanese subjects. All adverse reactions observed resolved without issue, and none required discontinuation from the study.

Bioequivalence of rebamipide granules and tablets in healthy adult male volunteers.

OBJECTIVE: Rebamipide tablets, which are used in the treatment of patients with gastric ulcers or gastritis, can be difficult to administer in subjects with reduced swallowing ability or impaired swallowing. The granule formulation may be more easily administered in these patients. The bioequivalence between rebamipide granules (20%/0.5g) and tablets (100mg) was determined in healthy male adult volunteers, in accordance with the Partially Revised Guidelines for Bioequivalence Studies of Generic Products. STUDY DESIGN: In a randomised, nonblind, crossover design, 28 individuals were allocated into two groups of 14 to receive either rebamipide granules or rebamipide tablets. Each individual, under fasting conditions, was administered a single oral dose of rebamipide 100mg followed by a 7-day washout period. Individuals then received a single oral dose of the other rebamipide formulation. Blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours. Plasma rebamipide concentrations were measured by validated high-performance liquid chromatography with tandem mass spectrometry. RESULTS: The plasma concentration-time profiles and pharmacokinetic parameters of rebamipide after administration of the granule formulation were similar to those of the tablet in 27 healthy male volunteers. Following administration of the granule formulation, the area under the plasma concentration-time curve from time 0-24 hours (AUC(24h)) was 912.82 mug/L . h, the maximum plasma concentration (C(max)) was 241.82 mug/L, time to maximum plasma concentration (t(max)) was 2.5 hours, and plasma elimination half-life (t((1/2))) was 1.97 hours. Corresponding values for the tablet formulation were 873.55 microg/L . h, 216.19 mug/L, 2.4 hours, and 1.94 hours. The difference in mean log values was 1.01 for AUC(24h) and 1.09 for C(max) after granule and tablet administration. The 90% confidence interval of this difference in mean log value was 0.93-1.10 for AUC(24h), and 0.97-1.21 for C(max). This satisfies the criteria for bioequivalence in the guidelines [within log (0.8) to log (1.25)]. CONCLUSIONS: Rebamipide granules (20%/0.5g) and tablet (100mg) were bioequivalent. Rebamipide granules may therefore be a more practical treatment option in patients with gastric ulcers or gastritis who have difficulty swallowing tablets.

Concentration of egg white lysozyme in the serum of healthy subjects after oral administration.

1. While the egg white lysozyme preparation ER0068 (Neuzym; Eisai, Tokyo, Japan) is widely used clinically, no studies have been performed on its pharmacokinetic properties at clinically relevant doses. In the present study, we used a highly sensitive two-site enzyme immunoassay in order to determine the pharmacokinetic properties of egg white lysozyme after oral administration of two doses within the clinical range, paying particular attention to the effects of food intake. 2. A total of 22 healthy male subjects aged 20-45 years participated in the study. All subjects had been screened for egg white allergy and non-specific lysozyme inhibitors in their serum. Subjects who received 90 mg ER0068 after an overnight fast reached a maximum serum concentration of 1700 pg/mL within 1 h, compared with non-detectable levels in untreated controls. In a second experiment, subjects received 30 and 90 mg ER0068 after an overnight fast and 90 mg in the non-fasted state and exhibited maximum serum levels of 37, 360 and 49 pg/mL, respectively. Egg white lysozyme concentrations in serum returned to undetectable levels after a maximum of 48 h. 3. We conclude that clinically relevant concentrations of egg white lysozyme are absorbed in significant amounts, despite its high molecular weight. However, food intake considerably reduces the amount of enzyme absorbed.