A simple method for monitoring radioactive contamination of imaging plates (IP) was proposed. IPs to be examined (IP_EX) were exposed under a standardized condition together with a few brand-new IPs used for correction of area dependency in background (IP_BG) and analyzed using a bio-imaging analyzer system (BAS). The background PSL values (PSL_BG) of each 5 × 5 mm area in an IP_EX were normalized with those of the corresponding area in IP_BG to obtain a normalized PSL_BG (PSL_BG(nor.)). The areas of radioactive contamination were identified by higher PSL_BG(nor.). The detection limit was approximately 6 mBq ¹⁴C/25 mm², when IPs were exposed for 72 hr in a 20 mm brass box. This proposed method makes it possible to retrace past information about radioactive contamination of an IP, when necessary.

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The absorption, distribution, metabolism and excretion of radioactivity were investigated after a single oral administration of 30 mg/kg of ¹⁴C-YM992 to rats.
1. Blood and plasma radioactivity levels reached the C_max at 30 min after administration, and then decreased bi-phasically with terminal half-lives (t_1/2) of 7.2 and 5.5 hr, respectively. Plasma unchanged drug levels reached the C_max 15 min after dosing, and then decreased bi-phasically with a t_1/2 of 1.2 hr. The ratios of the unchanged drug to total radioactivity level in the plasma were 1.6% and 4.1% at 5 and 15 min after dosing, respectively, and subsequently decreased to 0.1% at 8 hr after dosing.
2. ¹⁴C-YM992 was well absorbed from the duodenum to the colon but not stomach.
3. Radioactivity was distributed quickly into various tissues, showing a peak level within 1 hr after dosing in most tissues. Radioactivity levels (excluding the gastrointestinal tract) at 1 hr after dosing were highest in the liver, followed by the kidney, lung, adrenal, bone marrow, spleen, submandibular gland, and pancreas. Radioactivity disappeared relatively rapidly from most tissues, reflecting a decrease in the plasma concentration. The ratio of the unchanged drug to total radioactivity level in the cerebrum was 62.8% at 15 min after dosing, and subsequently decreased time-dependently to 33.3% at 24 hr after dosing.
4. Within 168 hr after dosing, 61.3% and 37.7% of the dosed radioactivity were excreted in the urine and feces, respectively. In bile-duct cannulated rats, 58.0 % and 39.4% of the dosed radioactivity were excreted within 72 hr in the bile and urine, respectively. At least 70.6% of the radioactivity excreted in bile was reabsorbed.
5. At least 18 peaks of radioactivity were observed in the radio-chromatogram of plasma at 1 hr after dosing, and at least 10 peaks in the radio-chromatograms of urine and bile collected for 6 hr after dosing. Little or trace amount of unchanged drug was observed in these samples. In the radio-chromatogram of cerebrum at 1 hr after dosing, at least 9 peaks of radioactivity were observed, and the main peak corresponded to the unchanged drug.

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The penetration and absorption of tacrolimus (FK506) in the skin of rat after a single topical application of ¹⁴C-labeled FK506 (¹⁴C-FK506) ointment under occlusive dressing was studied by semimicroautoradiography of the skin and by counting radioactivity in the sliced sections of the skin. Stability of FK506 in the skin was investigated in vivo and in vitro.
1. The distribution of the radioactivity of ¹⁴C-FK506 in rat skin was observed by semi-microautoradiography after a single dermal application of the ointment. In the intact skin, radioactivity of the ointment was mainly distributed in the stratum corneum of the epidermis during application for 24 hours. In the damaged skin, radioactivity was observed in the epidermis and dermis after application for 2 hours, and was evenly distributed in the dermis and subcutaneous connective tissues after application for 8 hours. Radioactivity was detected in the hair follicles of both the intact and damaged skin, but that was negligible in the sebaceous gland of the intact skin or was less than in the follicles of the damaged skin.
2. After a single dermal application of ¹⁴C-FK506 ointment to rats, the penetration of FK506 was investigated by counting radioactivity in the sliced section of skin. In the intact skin, maximal radioactivity was observed in the section of the epidermis throughout the application period for 24 hours. In the damaged skin, maximal radioactivity was detected in the dermis after application for 2 hours, and radioactivity in the sections was decreased thereafter and only a small amount of radioactivity was observed after application for 24 hours.
3. After application of ¹⁴C-FK506 ointment for 24 hours, levels of radioactivity were compared with those of FK506 in the skin, and the unchanged FK506 accounted for about 90% of radioactivity detected.
4. The oxidative metabolism of FK506 was studied in the skin and liver microsomes. Formation of the in vitro major metabolite, the 13-O-demethylated metabolite, in the skin microsomes was several-fold less intensive than in the liver microsomes.

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A new vehicle for a soft gelatin capsule with the basic formulation of PEG 400: water: medium chain triglyceride: polyoxyethylene (20) cetylether = 77: 10: 10: 3 was modified by partially replacing PEG 400 with PEG 6000 and added with vitamin K₂ as a model drug, and the effects of PEG 6000 on the stability of the vehicle and vitamin K₂ were studied for a period of 8 weeks at 4°C, room temperature and 40°C. For the vehicle containing 0.2% vitamin K₂ (a vitamin dose), temperature-dependent gel-sol transformation was prevented by replacing 2.0 or 3.0% of PEG 400 with PEG 6000, and the particle size distribution and appearance were maintained stable during 8 weeks of storage at each temperature tested. The vitamin K₂ was also found to be stable during the storage. Also for the vehicle containing 5.0% vitamin K₂ (a pharmacological dose), both of the vehicle and vitamin K₂, were found stable during 8 weeks of storage at every temperature. These results suggest that PEG 6000 plays an important role in maintaining the stability of vitamin K2 and the vehicle, preventing coagulation of particles, and this vehicle system could be used for preclinical and clinical trials.

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Since the discovery of morphine-6-glucuronide over three decades ago, an increasing body of work has emerged supporting the concept of an active metabolite in experimental animals and humans. Pharmacological characterization with antisense oligodeoxynucleotide of mu-opioid receptor, MOR-1 and receptor binding study have suggested the existence of an unique receptor of mu-subtype for morphine-6-glucuronide. In this review, our studies on species difference of site selective glucuronidation of morphine and UDP-glucuronosyltransferases responsible for the glucuronidation were presented. Recent experimental evidence supporting the view that UDP-glucuronosyltransferase isoforms could act as hetero-oligomers by accessing a broader range of substrates is included.

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