In the metabolism of drugs, as in chemical substances, acetylation is one example of the most common pattern of genetic polymorphism. We established an easy, rapid and specific method of distinguishing the genetic polymorphism of N-acetyltransferase, which is an application of the PCR-RFLP method, and is designed to be used in the clinical setting.
This method can extract deoxyribonucleic acid from a mouth mucous membrane sample, without the need to use an analysis kit or a blood sample. It was possible to clearly distinguish 4 alleles of N-acetyltransferase.

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The anticancer drug, dacarbazine, is known to be photosensitive, and its photode-gradation products have been pointed out as the causes of side effects including local venous pain of injection site. In this study, we attempted to clarify the causative sub-stance of pain after photodegradation of dacarbazine. We synthesized five photodegrada-tion products of dacarbazine dimethylamine, 5-diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 4-carbamoy1-2-(4-carbamoylimidazol-5-ylazo) imidazolium-5-olate and 2-azahypoxanthine, and examined pain reactions induced by these substances in mice. Mice were intraperitoneally administered each photodegrada-tion product, then number of stretching reactions or writhing reactions as types of pain behaviors was counted. Only Diazo-IC clearly induced the pain reactions in mice in a concentration-dependent manner the other products caused no pain reaction. The pain threshold of Diazo-IC in mice was estimated at between 0.1 mg/ml and 0.2 mg/ml. While diclofenac sodium significantly reduced acetic acid-induced pain reactions in mice, it did not influence the reactions induced by Diazo-IC. This result suggests that Diazo-IC-induced pain reactions represent a different mechanism from acetic acid-induced inflam-matory pain. Degradation rate constant of 0.1 mg/ml of dacarbazine solution was 10 times larger than 1 mg/ml of dacarbazine. Dacarbazine solution for drip infusion should be sufficiently shielded from light.

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Objectives: We investigated the effect of grapefruit juice (GFJ) on the pharmaco kinetics of the new nifedipine formulation, Adalat CR, which is a once-daily slow release (coat-core) tablet and is formulated to release nifedipine throughout the gastrointestinal tract.
Methods: Single doses of Adalat CR 20 mg and 40 mg were administered with 250 ml of GFJ (Kirin Tropicana^® 100%, Kirin Beverage Corp.) or water to eight Japanese healthy young male volunteers using the 4-treatment and 4-period crossover method with a 7-day washout period between treatments. Plasma concentrations of nifedipine and its metabolites (pyridine-form: M-I), and urinary metabolites (M-II and M-III) were measured.
Results: After administration of Adalat CR 20 mg and 40 mg with GFJ, the plasma concentration of nifedipine increased especially at the first peak of Adalat CR, which shows a two-peak profile. C_max and AUC were significantly increased by 59-80% and 13-23%, respectively and CL was significantly decreased by 12-19%. C_max ratio of pyridine-form to nifedipine (M I/nifedipine) was significantly decreased. Adalat CR was well tolerated even after administration with GFJ. No clinically relevant changes by GFJ were observed in blood pressure or pulse rate.
Conclusion: Changes in the pharmacokinetics after Adalat CR with GFJ were to a smaller extent compared to other dihydropiridines which are known interact with GFJ, i. e. nisoldipine or felodipine. Increased plasma concentration after administration of Adalat CR with GFJ was within the safe range. A marked interaction of Adalat CR with GFJ was not found. However, since C_max and AUC increased and CL decreased signifi cantly after the administration of Adalat CR with GFJ, it is recommendable to advise patients to avoid intake of GFJ when Adalat CR is administered.

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To attain good medication compliance is the major premise in well-controlled clinical trials. We conducted a questionnaire survey on 40 clinical investigators, 25 sponsors and 20 trial subjects during Oct.-Dec. 1998 to investigate the correlation among actual circumstances of medication compliance in trial subjects and the evaluation of medication compliance by clinical investigators and sponsors, and to determine effective measures to improve medication compliance. Whereas almost all clinical investigators and sponsors evaluated or expected over 70% of medication compliance, the trial subjects answered over 90%.
The clinical investigators (95%) and the sponsors (96%) thought in actuality that the primary means to maintain good compliance was for the clinical investigator to individually interview the trial subjects. The sponsors proposed possible adoption of clinical research coordinator's (CRC) support, a specific dispenser device or container, the use of medication diary, etc. However, only a few beneficial medication devices and medication diaries have been provided by the sponsors to date.
This survey suggests that the medicine dispenser device and the interview by CRC are very effective to attain good medication compliance.

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