The pharmacokinetics of adefovir dipivoxil, a novel reverse transcriptase inhibitor for the treatment of chronic hepatitis B, were investigated in healthy Japanese subjects (n=12) and Japanese patients with chronic hepatitis B (n=11).
Healthy males received single and multiple doses (once daily for 5 days) of adefovir dipivoxil 10 mg. After the first and final doses, blood and urine samples were collected over 48 hours and concentrations of adefovir, the hydrolysed active metabolite, measured by LC-MS/MS. Adefovir pharmacokinetic parameters (mean±SD) were comparable after single and multiple dosing: C_max 22.9±3.3 and 24.5±3.8 ng/mL, respectively. The single dose AUC _0-∞ (239.4±35.7 ng·hr/mL) and half-life (6.89±1.21 hr) were also similar to AUC _0-24 (249.3±32.9 ng·hr/mL) and t _1/2 (7.73±0.73 hr) after multiple dosing. The steadystate accumulation ratio was 1.05±0.12, indicating a lack of appreciable accumulation during multiple dosing. Approximately 60% of the dose was recovered in urine as adefovir.
Chronic hepatitis B patients with evidence of abnormal liver function associated with YMDD mutant hepatitis B virus and taking lamivudine 100 mg once daily were also studied. The results were similar to those in healthy subjects. C_max and AUC _0-∞ after the first dose of adefovir dipivoxil 10 mg in chronic hepatitis B patients were 20.1±3.3 ng/mL and 272.8±51.3 ng·hr/mL, respectively. Furthermore, the pharmacokinetics of adefovir were comparable in patients with and without cirrhosis. Adefovir pharmacokinetics in Japanese subjects with normal renal function are therefore not altered by chronic hepatitis B infection, lamivudine co-administration or the severity of hepatic disease. These Japanese results are consistent with those in Western subjects and a major inter-ethnic difference is not observed.

View full abstract

Since the importance of human tissue in the research for therapeutics and drug development has been widely recognized, the frequency of human tissue use for research has increased. The Human Science Research Resources Bank (HSRRB) has been established by the Japan Health Sciences Foundation as the first bank of human tissue for research in Japan. This public bank supplies human tissues for medical research to the scientists in Japan. To collect the human tissue for this bank, St. Marianna University School of Medicine has established an in-house institutional bank system as the human tissue supplier. The job clinical research coordinator, and a newly formatted informed consent and masking system of personal information by a special security manager have all been introduced, and high-quality tissue storage was installed for this system. The details of our system is described in the present paper; the problems encountered and countermeasures for such problems are also discussed.

View full abstract

It is likely that requests from hospital pharmacists to pharmaceutical companies are increasing with the greater sophistication and diversification of hospital pharmacist's practice in recent years. However, there is no nation-wide information concerning the requests to pharmaceutical companies. We surveyed the requests from hospital pharmacists to research laboratories of pharmaceutical companies by questionnaire. The questionnaires were sent to 42 national university hospitals, and 129 replies were received from pharmacists of 28 hospitals. Highly placed requests regarding drug developments included commercialization of in-hospital preparations (15.5%), commercialization of dosage forms taken easily (13.2%), improvement of packaging of medical products (24.8%), the addition of doses (19.4%) and expansion of therapeutic use of narcotics (8.6%). Hospital pharmacists requested a wide variety of information regarding effectiveness, safety, drug interactions, contraindication, instruction for use, patient instruction and guidelines. In the response calculations, 91.5 percent of hospital pharmacists wished to take part in drug development, but 68.2% of hospital pharmacists did not have contact with the research and development departments of pharmaceutical companies. These results suggest that it is necessary to establish close and bilateral exchange between hospital pharmacists and research and development departments of pharmaceutical companies in order to realize unmet hospital pharmacist's requests.

View full abstract

After the renovation of Good Clinical Practice (GCP), the industrial sponsors and medical institutions have improved their practice. However, the clinical trials greatly depend upon the understanding and cooperation of participating volunteers. The survey of Kobayashi et al. on Phase II/III Trials, revealed that participating patients generally had a good impression. We conducted a questionnaire on healthy volunteers to clarify whether a difference may exist.
Those who participated in a Phase I Trial after April 2001 at the six participating institutions were enrolled in the study. The questionnaire covered 31 topics related to the impression before and after participating in their first trial, general impression on the trial and others from between October 2004 and January 2005. Analysis of the data (without personal information) was conducted at St. Marianna University.
Healthy volunteers had almost the same impression of Clinical Trials as diseased patients in Phase II/III Trails. The study revealed that they wished for trials for new drug development to widely inform the public, and be carried out safely, but also in an active manner. We concluded that it is important to keep ourselves attentive to the public/volunteer opinion, and to continue to carry out good practice in Clinical Trials with a good relationship between and cooperation of volunteers and patients.

View full abstract