Effects of six antiallergic drugs on superoxide (O₂^-) production in xanthine-xanthine oxidase system were studied by the method of ESR spin trapping and measuring absorbance at 550 nm of ferricytochrome C.5 5-Dimethy1-1-pyrroline-N-oxide (DMPO) was used as a spin trapping agent.At the drug concentration of 600μM, only two drugs, tranilast (N-5') and amlexanox (AA-673), decreased significantly the signal intensity of DMPO-OOH adduct and the initial change in absorbance at 550nm per minute, indicating the O₂^- scavenging effect of these drugs.The O₂^- scavenging effect of AA-673 was stronger than that of N-5'. At the concentration of 30μM, it was recognized that AA-673 decreased O₂^-production more than 60% but not N-5'. These results indicate that AA-673 has the superoxide dismutase-like activity.

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We surveyed differences of curative rates of Yokuinin for verruca vulgaris between children and adults with a questionnaire.Curative rates of patients who belong to 0-5 years old, 6-11 years old, 12-17 years old, and over 18 years old were;71%, 74%, 56%, and 20%, respectively. The curative rate of patients over 18 years old was remarkably reduced as compared. with that of children under 12 years old.Significant difference was observed between the curative rate of 0-11 years old group and that of over 18 years old group.

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The morphine hydrochloride suppository (MoS) containing sodium caprate (CA-MoS) or.sodium 5-methoxysalicylate (MS-MoS) was studied physicochemically and biopharmaceutically.The hardness and melting point of such suppository freshly prepared or stored for 4 weeks were not affected by the absorption enhancers on comparison with those of MoS.The release of morphine from CA-MoS was much slower than that from MoS or MS-MoS.In the absorption experiments in vitro using the isolated rectal preparation of rabbit, percent of drug amount that was absorbed (i.e.accumulated in the tissue and permeated) after the application of MoS, CA-MoS and MS-MoS was 61.7, 63.1, and 86.5%, respectively. The rectal transport of morphine in vitro was significantly enhanced in the presence of sodium 5-methoxysalicylate. No histological change was observed in mucosal tissue of the rectum exposed to these absorption enhancers.

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Cisplatin suppositories were prepared with polyethylene glycol bases (PEG 1500, PEG 4000). The suppository released swiftly almost 100% of cisplatin within 90 minutes. On single intravenous administration to rabbits, blood levels of platinum decreased in a bi-exponential manner; the half lives of the α-and β-phase were 0.31 hours and 43.86 hours, respectively. On rectal administration of cisplatin suppository, the plasma concentration curve of platinum showed twocompartment model including the first-order absorption proccess.The absolute bioavailability of cisplatin suppository (AUC ^0→48 _suppo/AUC ^0→48 _i.v.×100%) was 24.5%.

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147 serum samples from epileptic patients under treatment with carbamazepine (CBZ) and/or phenytoin (PHT) and/or valproic acid (VPA) were obtained to study the correlation between total concentrations and free fractions, and the effect of antiepileptics coadministrated on the free fractions.CBZ free fractions were found to vary from 14 to 33%, and they were not effected by PHT or VPA coadoministrated. PHT free fractions were found to vary from 5 to 14%, but they increased significantly in the presence of VPA, and VPA and CBZ.There was no correlation between total concentrations and free fractions in PHT or CBZ, respectively.Whereas n VPA whose free fractions were found to vary from 4 to 18%, there was strong linear correlation between total concentrations and free fractions.However, the degree of variation of free fractions was not smaller even in lower total concentrations.In the serial monitoring of total concentrations and free fractions of antiepileptics in the same patients, there was the diurnal variation of free fraction, and the side effects were observed when the free fractions were higher.
From these results, it is necessary to monitor the serum free drug concentrations rather than total drug concentrations for deciding the dosage when as follows:(1) In patients concomitantly taking PHT and VPA, or VPA and CBZ, (2) In patients taking VPA which reveals the wide variation of free fractions in serum, and (3) In patients who are difficult to control clinical conditions even though total concentrations are in the therapeutic level and in the steady states.

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