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Biomedical subjects

K Sunakawa

Publications and source records attributed to K Sunakawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

[The intractable bacterial infection in the pediatric field].

In recent years, medical treatment of neonates, especially premature infants, has made a remarkable progress, but the rate of neonatal mortality from bacterial infection has not decreased. Our early diagnosis and treatment of neonatal bacterial infection was discussed as below, 1) The rate of onset of neonatal sepsis was higher in neonates under 1500 gr birth weight, and a trend for increase of E. cloacae, which is the main causative organism of sepsis in recent years, was recognized. 2) The intestinal tract, skin, and some kinds of catheters were suggested as the main root of sepsis. Therefore the following three points, namely, selection of antibiotics which has less influence in the intestinal flora, early treatment of skin infection, and regular culture of surveillance are highly important in early diagnosis and treatment and prevention of infections.

Bacteremia↗
PubMed1994

[Pharmacokinetic and clinical studies on fluconazole in the pediatric field].

Pharmacokinetic, bacteriological and clinical studies on intravenous fluconazole (FLCZ) in deep seated mycoses were performed involving 4 pediatric patients. Clinical and bacteriological assessments were made on 4 patients; clinical improvements were good in 3 patients and bacteriological efficacies were rated as "eradicated" in 3 patients. No side effects nor abnormal laboratory values were observed. The pharmacokinetics were investigated in 2 patients. Good serum FLCZ concentrations were obtained at an intravenous dose of 3-6 mg/kg daily. These results indicate that FLCZ is a useful drug in the treatment of pediatric patients with systemic deep-seated mycosis.

Adolescent↗
PubMed1993

[Inhibitory effects of palonidipine hydrochloride (TC-81) on contractions induced by various vasoconstrictors in rat aorta].

Inhibitions by palonidipine hydrochloride (TC-81), a new Ca entry blocker, of the contractile responses to norepinephrine (NE), serotonin (5-HT), prostaglandin F2 alpha (PGF2 alpha) and U-46619, a thromboxane A2 analog, were investigated in isolated rat aorta strips and compared with the inhibition of the high K+ response. TC-81 and nicardipine inhibited the contractile responses to NE, 5-HT, PGF2 alpha, and U-46619 in a concentration-dependent manner, but their relative inhibitions were less than 50% at 10(-8) M. In a Ca(2+)-free medium, 2-hr pretreatment with TC-81 or nicardipine did not inhibit the contractile responses to various vasoconstrictors, but it inhibited the responses to the addition of Ca. Their inhibitory potencies were less than the inhibition with high K+. Also, the treatment with TC-81 or nicardipine at 10(-7) M did not affect the tissue level of cyclic AMP. These results suggest that in isolated rat aorta, the inhibition by TC-81 of the contractile responses to NE, 5-HT, PGF2 alpha and U-46619 is not due to inhibition of intracellular Ca2+ release or an increase in cyclic AMP; rather, it is due to inhibition of the Ca2+ influx. This inhibitory effect was less than that seen on the high K+ response.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

[Effect of palonidipine hydrochloride (TC-81), a novel calcium antagonist, on the canine coronary artery].

The effects of palonidipine hydrochloride [TC-81: (+/-)-3-benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride], a new calcium antagonist, on the coronary artery were studied in dogs. In the isolated canine coronary artery, TC-81 inhibited high K+ (60 mM)-induced contraction in a concentration-dependent manner. The relaxant activity of TC-81 was equal to that of nicardipine and more potent than those of nifedipine and diltiazem. TC-81 increased coronary blood flow in a dose-dependent manner after i.v.-administration in anesthetized open-chest dogs. The activity of TC-81 was equal to that of nifedipine or nicardipine, but the duration of its effect was longer than that of nifedipine or nicardipine. By oral administration in conscious dogs, TC-81 increased coronary blood flow at 0.1 mg/kg or more, and its activity was 10 times more potent than that of nifedipine. These results suggest that TC-81 increases coronary blood flow and is capable of improving the oxygen supply-demand relationship during angina pectoris.

Animals↗
PubMed1993

[Influence of S-1108 on intestinal bacterial flora].

The effect of S-1108, a new oral cephem antibiotic, on intestinal bacterial flora was studied in tetra-contaminated mice and pediatric patients. S-1108 in a fine granular form was administered at a dose of 15 mg/kg once a day for 5 consecutive days to mice infected with Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. The viable fecal bacterial cell count of each of these 4 species of bacteria was slightly reduced in 5 days after the start of the drug administration. Five boys (weighing 12.0 to 42.0 kg) with bacterial infections were entered into this pediatric study. Their ages ranged from 2 years 4 months to 9 years 3 months. S-1108 (fine granules) was administered at a dose of 2.3 to 6.0 mg/kg, 3 times a day for 5 to 11 days. Cell counts of primary aerobes, anaerobes and total anaerobic cells decreased markedly in three patients, but in the remaining two patients the total number of aerobic and anaerobic cells did not change appreciably. Glucose-nonfermentating Gram-negative rods did not become predominant during the period of S-1108 administration. Candida became predominant in the three patients in whom the other bacteria had markedly decreased. Counts of predominant aerobic and anaerobic bacteria decreased markedly during the regimen in 3 out of 5 cases. S-1006 was detected in stools of the 3 cases at concentrations ranging from 235 to 516 micrograms/g during the administration of S-1108. Intestinal bacteria that produce beta-lactamase were not present in the feces of any of the patients. Based on these results, S-1108 (fine granules) appears to have relatively little effect on intestinal bacterial flora similarly to other new oral cephems. Because of individual differences, however, the drug may be excreted in the feces at high concentrations, and this would result in changes in intestinal bacterial flora. Therefore, attention must be given to fecal drug concentrations.

Administration, Oral↗
PubMed1993

[A clinical study of fluconazole-granules and -injectable in pediatric patients with deep-seated mycoses].

Fluconazole (FLCZ) is an antifungal agent of triazole class developed by Pfizer, Inc. Its oral and injectable forms have been available on the market since June 1989 in Japan. FLCZ exhibits potent antifungal activities against Candida spp., Aspergillus spp. and Cryptococcus spp. and, as orally or intravenously administered, is widely distributed into organs and tissues. For its low protein binding rate of about 10 per cent and long serum half life of about thirty hours in adults, FLCZ has been proved highly effective and useful in the treatment of deep-seated mycosis in adult patients. In the present study, we have investigated the clinical effectiveness and antifungal activities of FLCZ granules, a new dosage form of the drug, and of intravenous form in pediatric patients with deep mycosis. A total of 72 patients were treated either with granules orally or with intravenous injection and 47 patients among them were evaluable on the clinical efficacy of the drug. Also, a study on the pharmacokinetics of pediatric patients including premature/new born babies was conducted employing multiple dose regimens in a total of 27 patients. The clinical efficacy rates were 79.5% (35 patients out of 44) in candidiasis and 100.0% (3 of 3) in aspergillosis. The safety of the drug was assessed in 63 patients. No side effects were observed. Clinical laboratory test abnormalities were observed in some patients with an incidence of 9.7% (6 patients out of 62) but most of the abnormalities were only mild and transient. The pharmacokinetics at repeated doses indicated that a steady-state is reached in 4 days after the initial administration of either granules or intravenous form. From these results, it may be concluded that FLCZ is a very useful medication in the treatment of deep mycosis in pediatric patients.

Administration, Oral↗
PubMed1993

[Criteria for clinical evaluation of antibiotics in pediatrics. The purpose and process for establishing the criteria].

This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol. 46, May, 1993. The Criteria Committee was organized in November 1991. Four meetings were held to establish the draft criteria. The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787. When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent". Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria. However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.

Bacterial Infections↗
PubMed1993

[Effect of cefditoren pivoxil on carnitine metabolism in pediatric patients].

Carnitine metabolism was studied in 16 pediatric patients with various infections under the treatment with cefditoren pivoxil (CDTR-PI) in granular form. Pivalic acid released from pivaloyloxymethyl ester of the drug was metabolized to pivaloylcarnitine. As results, an increase in urinary carnitine excretion (predominantly as pivaloylcarnitine) and, a decrease in free carnitine concentration and a high acyl/free carnitine ratio in serum (plasma) were observed during the treatment. When the dosing was terminated, pivaloylcarnitine in plasma and then in urine disappeared, and the concentration of free carnitine, acyl/free carnitine ratio returned to the normal range. No carnitine-related side effects were observed throughout the study.

Bacterial Infections↗
PubMed1993

[Laboratory and clinical studies on S-1108 in the pediatric field].

Laboratory and Clinical Studies on S-1108, a new oral cephem antibiotic, were carried out to evaluate its usefulness at a dose between 2 and 4 mg/kg a day for 7 to 14 days in the pediatric field. 1) Pharmacokinetic studies S-1108 at a dose of 2 mg/kg was administered to evaluate the pharmacokinetic parameters in 1 subject. Cmax, T1/2 and AUC were 0.69 hour, 1.42 hours and 2.15 micrograms.hr/ml, respectively. 2) Antimicrobial activities MICs against various clinically isolated organisms (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Branhamella catarrhalis, Escherichia coli and Haemophilus influenzae) were determined. The MIC values of S-1006 were similar to those of cefteram, the MICs against S. pyogenes, and H. influenzae were < or = 0.025 and 0.10 microgram/ml, respectively. 3) Clinical studies S-1108 was administered to patients with various pediatrics infections in 34 cases (upper respiratory tract infections: 12 cases, lower respiratory tract infections: 5 cases, urinary tract infections: 9 cases, skin and soft tissue infection: 6 cases, otitis media: 2 cases). Clinical efficacy rate was evaluated according to "Standard of clinical evaluation in pediatrics field". The responses were all good or excellent. 4) Side reactions There were no serious adverse reactions in any cases. The above results suggest that S-1108 is potent effective and safe agent in the pediatric field at a dose between 2-4 mg/kg (t.i.d.) a day.

Bacteria↗
PubMed1993

[A clinical study on cefditoren pivoxil in pediatrics].

Clinical evaluations of cefditoren pivoxil (CDTR-PI, ME 1207) in granules were carried out. The obtained results are summarized as follows. 1. Thirty-nine patients with pediatric infections were treated with CDTR-PI. Clinical responses of 36 assessable cases were excellent in 25, good in 9 and fair in 2. The overall efficacy rate was 94%. 2. Bacteriologically, 30 of the 31 identified bacteria presumed to be pathogens were eradicated and the eradication rate was 97%. 3. Side effects observed were diarrhea in 3 of 39 patients. The incidence was 7.7%. Abnormal laboratory test results were not observed. The results suggested that CDTR-PI might be a very useful and safe drug for the treatment of pediatric infections.

Bacterial Infections↗
PubMed1992

Differences in responses to TC-81 among various arteries in dogs.

The vasodilation induced by TC-81 was investigated in vitro and in vivo. In helical strips of dog arteries precontracted with 65.4 mM KCl, TC-81, nicardipine, nifedipine, diltiazem, and papaverine produced concentration-dependent relaxation. The potencies of TC-81 were in the following order: basilar > coronary > femoral > renal > mesenteric arteries. The other drugs also showed a similar property of greater response in basilar and coronary arteries than in renal and mesenteric arteries. However, the difference in reactivity to TC-81 was greater. On the other hand, TC-81, nicardipine, and papaverine dose-dependently increased the blood flow in vertebral, coronary, and femoral arteries in anesthetized dogs. However, the blood flow in renal and mesenteric arteries was not changed or decreased. The decreases in vessel resistance induced by TC-81 were in the following order: vertebral > coronary > femoral > renal = mesenteric arteries, agreeing with the experimental results in vitro. These results suggest that Ca2+ antagonists have the pharmacological property of vasodilating cerebral and heart blood vessels more selectively than other arteries, and this property of TC-81 might be an advantage compared with other drugs.

Animals↗
PubMed1992

Synthesis and antihypertensive activity of 1,4-dihydropyridine derivatives with a 4-(disubstituted phenyl) ring and an aminoalkyl ester group: highly potent and long-lasting calcium antagonists.

New 1,4-dihydropyridine derivatives bearing a 4-(disubstituted phenyl) ring and an aminoethyl ester or an amino-2,2-dimethyl-propyl ester were synthesized and their antihypertensive activities were examined in normotensive rats and spontaneously hypertensive rats. The effects of phenyl substituents and ester groups on the antihypertensive activity are discussed. Several compounds showed a more potent antihypertensive activity than nicardipine and most compounds had a longer duration of action. Among them, 7B.HCl (TC-81) showed highly potent and long-lasting activity and was selected as a candidate for further pharmacological investigations.

Animals↗
PubMed1992

Effects of inline filtration on delivery of gentamicin at various flow rates.

The effects of inline filtration on delivery of gentamicin (GM) in the pediatric field were studied. The filter sets (Pall 0.20 micron. JMS 0.20 micron, and IVEX 2.022 micron) were studied using a simulated system. 10 mg of GM was injected into the system containing 5% dextrose in water (flow rate: 50 ml/hr, 10 ml/hr and 2 ml/hr) with horizontal and vertical settings of the inline filters. In case of 50 ml/hr, delivery of GM of Pall showed nearly the same delivery pattern as compared with no filter setting. However, JMS and IVEX 2 showed little differences. In case of 10 ml/hr and 2 ml/hr those differences became more significant. Delivery of GM was influenced by the priming volume of the filters, increasingly so at slow flow rates. Filter settings also influenced the delivery of GM. Furthermore, with regards to the results of the Vitamin K2 delivery and the technetium radiotracer method, JMS and IVEX 2 filters were observed to have some stagnation of drugs in the filter. Not only priming volumes of the filters affect delivery of drugs, filter designs also have an influence. The use of the inline filters is important in the pediatric field, but their charactaristics for drug delivery pattern should be considered.

Drug Contamination↗
PubMed1992

[Effect of meropenem on fecal flora in children].

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.

Age Factors↗
PubMed1992

[Laboratory and clinical studies on cefprozil granules in pediatrics].

Fundamental and clinical effects of cefprozil (CFPZ, BMY-28100) granules, a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows. 1. CFPZ (10% granules) was given to 1 child in a single dose of 7.5 mg/kg. The peak serum concentration of CFPZ was 4.51 micrograms/ml at 2 hours after administration. Half-life and AUC values were 0.98 hour and 20.7 micrograms.hr/ml. The mean peak urinary concentrations of CFPZ and 6 hours recovery rates were over 200 micrograms/ml at 2-6 hours and 27.6%, respectively. 2. Clinical efficacy of CFPZ was investigated in a total of 41 children, including 14 with upper respiratory tract infections, 6 with acute bronchitis and pneumonia, 2 with acute otitis media, 3 with skin and soft tissue infections and 16 with urinary tract infections. The clinical efficacy rate was 95.1%. The bacteriological eradication rate was 84.6%. 3. Two patients showed abnormal laboratory test results. One had elevations of both GOT and GPT, and another had eosinophilia which were attributed to this antibiotic as side effects.

Bacteria↗