Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics.

Three major traditional Chinese medicines (TCM), Sho-saiko-To, Saiboku-To, and Sairei-To, consist of similar herbal prescriptions containing glycyrrhizin, which is a strong inhibitor of 11 beta-hydroxysteroid dehydrogenase. We performed cross-over open trials in healthy subjects to clarify prednisolone pharmacokinetics on co-administration of these preparations. All subjects received a single oral dose of 10 mg prednisolone before oral treatment with one of the test preparations. After a 2-week wash-out interval, they received one of the test preparations for three days at daily doses of 7.5 or 9.0 g. On the third study day, 10mg prednisolone was administered orally in combination with the test preparation. Area under the curves (AUC) of prednisolone before and after the treatment decreased from 0.94 to 0.78 mg h L-1 (P < 0.05) in the Sho-saiko-To group, increased from 0.92 to 1.06 mg h L-1 (P < 0.01) in the Saiboku-To group, and did not change in the Sairei-To group. AUC ratios of prednisone and prednisolone, which reflect the 11 beta-hydroxysteroid dehydrogenase activity, increased in the Sho-saiko-To group (P < 0.01), decreased in the Saiboku-To group (P < 0.01), and did not change in the Sairei-To group after the treatments. Similar results were observed in ratios of endogenous cortisone to cortisol. Because of the equal glycyrrhizin content in all three preparations, it was unexpected that the 11 beta-hydroxysteroid dehydrogenase effect was different amongst the three groups. These observations suggest that some unknown metabolic enzyme modifiers, promoters or inhibitors, may be involved in these traditional treatments.

[Optimal calcium concentration for the proliferation of oral mucosal epithelial cells from adult rabbit in vitro].

We studied a primary culture of oral epithelial cells from adult rabbit and reported about dose-dependent growth by Ca increase. Therefore, in the present study we examined the relationship between total Ca, or Ca ion concentration and the proliferation of oral epithelial cells. The results were as followings. 1. The optimal Ca concentration for the growth in primary culture of oral epithelial cells was affected by the serum concentration in the medium. But Ca ion concentration for the best growth was in 10-30 micrograms/ml (0.25-0.74 mM) regardless of the serum concentration. 2. The optimal Ca ion concentration was shifted to 3-20 micrograms/ml (0.075-0.5 mM) in the medium containing chelated serum. This fact, suggests that the chelated serum may play different action from whole serum. 3. The optimal Ca ion concentration in the present study was higher density region than Hennings's view (0.04-0.1 mM) and it was lower than that of Tong (1.4-2.8 mM). Our data coincided with that of Wille (0.18-0.36 mM) who used MCDB 153 medium.

Effects of chelated sera and alteration in calcium concentration on the growth of oral epithelial cells in primary culture.

The purpose of this study were to examine the distribution of growth-promoting activity of some chelated sera and to investigate the relationship between calcium concentration in culture medium and the growth-promoting activity of the chelated sera in comparison with that of the original serum. Results showed that the chelated serum obtained by acidic resin treatment promoted colony formation, while the number of colonies decreased in cultures containing either dialyzed serum or chelated one obtained by treatment with alkaline resin. The acid-chelated serum and its lyophilized materials maintained the growth-promoting activity for 6 months or more in a deep freezer. This activity depended on the calcium concentration of culture medium in the range from 0.06 to approximately 1.5 mM. The optimal concentration of this material for growth promotion was 4 mg/ml as the protein density, which was about a quarter of that for the original serum protein. Sera from different sources treated with the acidic resin also showed similar effect on the growth. This finding strongly suggests that the acid-chelated serum and its lyophilized protein contain a keratinocyte growth factor(s).

[Clinical evaluation of roxithromycin in odontogenic infection].

The clinical effectiveness and safety of roxithromycin (RU 28965, RU), a new macrolide antibiotic, were compared with those of josamycin (JM) using a double-blind method in the treatment of orofacial odontogenic infections. The diseases covered in this study were periodontal infections, pericoronal infections and osteitis of jaws. Drugs were administered for 3 to 7 days at daily doses of 300 mg (RU) and 1,200 mg (JM). A total of 270 cases was evaluated in this study. Results obtained are summarized as follows: 1. The clinical efficacy was evaluated through the judgement of doctors in charge of 247 cases (128 in the RU group and 119 in the JM group) and by a committee on the 3rd day of treatment in 243 cases (126 in the RU group and 117 in the JM group). Clinical efficacy rates according to the committee judgement were 78.6% for the RU group and 82.1% for the JM group. As for the evaluation through the doctors' judgement, they were 79.7% for the RU group and 73.1% for the JM group. There was no significant difference in clinical effectiveness between 2 groups according to these 2 methods of judgement. 2. Some side effects were observed in 4 cases (2.9% out of 136) treated with RU and in 3 cases (2.4% out of 126) treated with JM. No severe symptoms were observed. Abnormal changes in laboratory test values were noted among 7.9% in the RU group and 4.0% in the JM group. There were no significant differences in their safety between the 2 groups. 3. In terms of clinical usefulness, there were no significant differences between the 2 groups as well. From these results, it has been concluded that RU (daily dose 300 mg) is as effective as JM (daily dose 1,200 mg) in the treatment of orofacial odontogenic infections.

[Clinical evaluation of clarithromycin in treatment of acute dental infections. Comparative double-blind study using josamycin as the control].

In order to objectively evaluate the usefulness of clarithromycin (TE-031, A-56268), a new oral macrolide antibiotic, in the treatment of acute dental infections, a double-blind comparative clinical trail was conducted using josamycin (JM) as the control drug. TE-031 was administered at a daily dosage of 400 mg in 2 divided doses, and JM was given at a daily dosage of 1,200 mg in 3 divided doses. The administration period was, as a rule, 7 days. A total of 302 patients were administered with the test substances (TE-031 and JM), and the clinical efficacy was evaluated by investigators for 284 patients and by a committee using a score method for 273 patients. Efficacy rates as evaluated by the investigators were 77.2% (105/136) in the TE-031 group and 69.6% (103/148) in the JM group. Efficacy rates as evaluated by the committee by the score method were 86.0% (111/129) in the TE-031 group and 80.6% (116/144) in the JM group. The differences between the 2 drug groups were not statistically significant. The investigators' evaluation of the clinical efficacy in the treatment of osteitis of the jaw gave an efficacy rate of 83.0% (44/53) in the TE-031 group and 64.7% (33/51) in the JM group. The efficacy rate in the TE-031 group was statistically higher than that in the JM group. Side effects were recorded in 7 patients (4.8%) in the TE-031 group and 3 patients (2.0%) in the JM group, while abnormal laboratory test values were detected in 3 cases each in the TE-031 and JM groups. None of these differences were statistically significant. The usefulness rates ("satisfactory" plus "very satisfactory" cases) were 73.9% in the TE-031 group and 70.3% in the JM group and were thus almost the same for the 2 drug groups. On the basis of the above results, TE-031 was concluded to be a useful drug in the treatment of acute dental infections and is expected to be able to achieve almost identical clinical efficacy as JM at only one-third of the usual dosage of JM.

[A comparative double blind study of lenampicillin and talampicillin in the treatment of oral infections].

A comparative double blind study of lenampicillin (LAPC, KBT-1585) and talampicillin (TAPC) was carried out in order to objectively evaluate efficacy, safety and utility of LAPC in treatment of 238 patients with oral infections. Cases accepted by the Central Committee for evaluation of efficacy and utility were 218, consisting of 101 of the LAPC group and 117 of the TAPC group; safety were 234, consisting of 110 of LAPC and 124 of TAPC. Clinical effectiveness as rated by attending doctor was 84.2% for the LAPC group and 82.9% for the TAPC group. The clinical utility rating was 82.2% in the LAPC group and 82.1% in the TAPC group, showing no significant difference between the 2 drugs. Adverse reactions were found in 6 cases (5.5%) in the LAPC group and 5 cases (4.0%) in the TAPC group, showing no significant difference between the 2 drugs. Cases accepted by the controllers for evaluation of efficacy and utility were 236, consisting of 111 cases of LAPC and 125 cases of TAPC. Those for safety were 236, consisting of 111 cases of LAPC and 125 of TAPC. The clinical effectiveness rating was 77.5% in the LAPC group and 79.2% in the TAPC group. Clinical utility rating was 75.7% in the LAPC group and 78.4% in the TAPC group. Rate of adverse reactions was 5.4% in the LAPC group and 4.0% in the TAPC group, showing no significant difference between the 2 drugs. Cases evaluated for efficacy according to numerical rating on the 3rd day were 200 cases, consisting of 93 of LAPC and 107 of TAPC. The effectiveness rate was 83.9% in the LAPC group and 95.3 in the TAPC group, showing a significant difference between the 2 drugs. On the other hand, taking into consideration evaluation scores of the 5th day, the effectiveness rate was 88.7% in the LAPC group and 96.1% in the TAPC group, showing no significant difference between the 2 drugs. The effectiveness rate in cases of isolated organisms was 84.9% in the LAPC group and 79.7% in the TAPC group, showing no significant difference between the 2 drugs. Adverse reactions were mostly of gastrointestinal origin. Symptoms were not serious and disappeared soon after administration was discontinued or immediately after administration was completed.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical evaluation of the TMS-19-Q.GC tablet in odontogenic infections. A comparative double-blind study with josamycin].

Clinical efficacy and safety of TMS-19-Q.GC tablet (TMS), a new macrolide antibiotic preparation, were compared with those of josamycin (JM) in the treatment of acute odontogenic infection under multicentered double-blind controlled study at the daily dosage of 600 mg of TMS or 1,200 mg of JM. The results obtained were as follows: The patients entered into the study were 265 cases and 112 in TMS group and 111 in JM group were adopted to evaluate for the efficacy. The evaluation was made by 2 ways i.e. changes in total clinical scores of the symptom and the doctors assessment. Efficacy rating of TMS and JM were 81.3 and 82.0% judged by the score and 73.2 and 77.5% judged by doctors in charge respectively. In the cases with 15 to 20 of total scores at the initial visit, considered to be suitable for the evaluation of antibiotics, the efficacy rating of both drugs were 86.7% in TMS and 84.6% in JM. Organisms were isolated from 34 cases in TMS and 40 in JM and the clinical effectiveness in those cases were almost the same. Slight adverse reactions were observed in 6 cases (4.6%) of TMS group and 1 (0.8%) of JM. In 3 cases (4 incidences) of TMS group and 1 of JM slightly abnormal laboratory findings were found. On the statistical analysis of the data regarding efficacy, safety and usefulness, both drugs had no significant difference. From these results, TMS was considered as effective as JM in the treatment of acute odontogenic infection at a daily half doses of JM.