Biomedical subjects

Yasuhiko Ogura

Publications and source records attributed to Yasuhiko Ogura.

3 recordsLinked to original sources

PubMed2004

Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies.

The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1 mg to 2.5, 5, 10, or 20 mg. Subsequently, risedronate was given by multiple administration, 5 mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary Beta(2)-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20 mg or as a multiple administration of up to 5 mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C(max), after the administration of risedronate at 1, 2.5, 5, 10, and 20 mg, increased dose dependently, and the T(max), t(1/2), and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20 mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5 mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5 mg risedronate to the United Kingdom study population.

Administration, Oral↗

PubMed2004

Clinical trial of risedronate in Japanese volunteers: a study on the effects of timing of dosing on absorption.

Because of its chemical structure, risedronate was thought to form a complex with divalent cations, e.g., Ca(2+), and to be likely to show changes in the efficiency of absorbance from the gastrointestinal tract according to the presence of food. Therefore, we conducted a crossover study using healthy Japanese adults to examine the effects of food intake on absorption after the oral administration of risedronate and to choose the best timing of regimen for risedronate. Using single doses of 5 mg risedronate, the following four dose times were investigated: (a) in the morning under a fasting condition without breakfast; (b) 30 min before breakfast; (c) 30 min after breakfast; and (d) 3 h after breakfast. The results showed that the C(max) and AUC(0-24) of the plasma risedronate concentrations and its cumulative urinary excretions decreased in the following order: fasting without breakfast >>30 min before breakfast >>3 h after breakfast >>30 min after breakfast. In other words, it was demonstrated that the absorption of risedronate decreases due to the effects of food. Several adverse events, whose causality with risedronate was unknown or possibly related, were observed, including headaches, diarrhea, increased CK-BB, and an increased urinary Beta(2)-microglobulin excretion rate, but none of these events was clinically significant, and none differed in frequency or severity from the events after a single oral administration. In consideration of the optimal practical timings required to administer risedronate for Japanese patients, therefore, it was found that ingesting the drug immediately after waking up in the morning, when the stomach is empty, was optimal, and that it was necessary to refrain from eating and drinking for at least 30 min after drug ingestion. Therefore, we determined that the optimal time for risedronate to be administered in Japanese patients is 30 min before breakfast.

Administration, Oral↗

PubMed2002

[Risedronate].

Risedronate has recently been approved as a drug for osteoporosis treatment in Japan. According to its chemical structure, risedronate is designated a third generation bisphosphonate, which has potent anti-resorptive activity. Clinical studies conducted in Japan, North America and/or Europe revealed that risedronate reduces the risks of hip fractures and vertebral fractures by around 30% and around 50% compared with placebo over three years, respectively, and increases lumber spine BMD by around 5% at one year after starting treatment. In addition, risedronate produces a rapid and clinically important reduction in the risk of vertebral fracture and bone formed during risedronate treatment was histologically normal. Bone turnover markers, e.g., deoxypyridinoline, NTx, are reduced by around 40% (maximum). Although some bisphosphonates have been associated with upper gastrointestinal (GI) tract adverse events, a pooled analysis of 9 placebo-controlled clinical trials conducted outside Japan revealed no evidence that risedronate was associated with an increased frequency of adverse effects in the GI tract when compared with placebo.

English Abstract↗