Biomedical subjects
Publications and source records attributed to C Ikeda.
The case of a 17-month-old girl with fulminant meningococcemia is presented to illustrate the protean and fulminant course of the disease. Special attention is given to the meningococcal skin manifestation, with guidelines for its treatment.
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Use of a fish hook-shaped needle electrode for electrocardiographic monitoring in burn patients is described.
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The pharmacokinetics of cefpiramide (SM-1652) were studied after the intravenous administration of single or multiple doses to 21 healthy volunteers. The cefpiramide concentration in plasma at time zero after a bolus intravenous injection of 500 or 1,000 mg was 152 or 303 micrograms/ml, respectively. The maximum cefpiramide level in plasma at the end of a 1-h infusion of 1,000 or 2,000 mg was 166 or 317 micrograms/ml, respectively. The mean plasma half-life of cefpiramide in 15 subjects who received a single dose of 500 or 1,000 mg was 4.44 h. There was no evidence of drug accumulation in plasma when 500 or 1,000 mg of cefpiramide was administered 11 times at 12-h intervals. Urinary excretion of cefpiramide over a 24-h period was ca. 22.5%, regardless of the intravenous administration technique and the dosage. Fecal recoveries of cefpiramide varied from 0 to 36.9% in different subjects.
The pharmacokinetics of YM-13115, ceftriaxone, and ceftazidime were studied in rats, dogs, and rhesus monkeys (only YM-13115 and ceftriaxone were studied in rhesus monkeys). The plasma half-lives in rats were 48 min for YM-13115, 34 min for ceftriaxone, and 14 min for ceftazidime. In dogs, they were 21.9 min for YM-13115, 50.7 min for ceftriaxone, and 49.0 min for ceftazidime. In monkeys, they were 5.30 h for YM-13115 and 3.40 h for ceftriaxone. The 24-h urinary recoveries in rats were 26.7% of the dose for YM-13115, 32.0% for ceftriaxone, and 97.1% for ceftazidime. In dogs, they were 13.3% for YM-13115, 62.5% for ceftriaxone, and 86.3% for ceftazidime. In monkeys, they were 22.5% for YM-13115 and 29.3% for ceftriaxone. The 24-h biliary recoveries in rats were 72.2% for YM-13115, 61.8% for ceftriaxone, and 0.63% for ceftazidime.
Chicamycin is a new antitumor antibiotic produced by a strain of Streptomyces albus, No. J576 -99. The antibiotic is extractable into organic solvents from the fermentation broth and is obtained in two active forms, chicamycins A and B, depending upon the isolation procedure used. Chicamycin A is not a natural antibiotic but the methanol adduct of naturally produced chicamycin B. Both forms of the antibiotic have weak antibacterial activity against some Gram-positive and acid-fast bacteria. They inhibit the growth of experimental tumors such as P388 mouse leukemia.
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The beta-lactam and aminoglycoside groups of antibiotics are often used in combination. This paper reports a bioassay method for each of cefotetan and sisomicin concentration in body fluids, and pharmacokinetics of both drugs following intravenous administration of cefotetan and intramuscular administration of sisomicin alone and in combination to rats. As to cefotetan determination, a previously reported bioassay method was modified by increasing the NaCl concentration in the sensitivity test agar from 0 to 6%, using Bacillus subtilis ATCC 6633 as the test organism. To assay for sisomicin in the presence of cefotetan, Pseudomonas aeruginosa ATCC 8689, resistant to the beta-lactam antibiotic, was used. Cefotetan (20 mg/kg intravenous) and sisomicin (10 mg/kg intramuscular) were administered concomitantly to rats. The mean plasma concentrations of cefotetan and sisomicin were 16.3 microgram/ml and 16.1 microgram/ml, at 30 minutes after administration respectively. The concentrations were declined to 2.20 microgram/ml for cefotetan and 2.53 microgram/ml for sisomicin at 90 minutes after dosing administration. The calculated plasma half-lives (T 1/2 beta) were 21.3 minutes for cefotetan and 22.2 minutes for sisomicin. The plasma and tissue concentrations of cefotetan administered in combination with sisomicin were nearly the same as those of cefotetan alone. Urinary excretion of cefotetan and sisomicin in the concomitant administration was carried out in rats. Recoveries in urine were 45.9% of the dose for cefotetan and 85.6% of the dose for sisomicin for a period of 24 hours. When each drug was administered alone to rats, cefotetan and sisomicin were recovered 49.8% and 81.6%, respectively, of the dose in the 24-hour urine.
Cefotetan (20 mg/kg i.v.) and sisomicin (10 mg/kg i.m.) were administered alone or in combination to Beagle dogs. The mean plasma concentrations of cefotetan administered in combination with sisomicin at the above dosages were 98.0 microgram/ml at 5 minutes, 45.7 microgram/ml at 30 minutes and 3.46 microgram/ml at 4 hours. These plasma concentrations of cefotetan were similar to those of cefotetan administered alone to the corresponding dogs. The calculated plasma half-lives (T 1/2 beta) of cefotetan were 53.9 minutes in combination with sisomicin and 57.4 minutes alone. The excretion of cefotetan in dog urine were 52.4% and 50.2% of the dose after administration in combination with sisomicin and alone, respectively, during 24 hours. The results indicate that there were no significant differences in the pharmacokinetics of cefotetan alone or in combination with sisomicin in dogs. The maximum concentrations of sisomicin in dogs administered in combination with cefotetan were 20.2 microgram/ml at 30 minutes after dosing. The concentrations of 11.7 microgram/ml at 2 hours and 3.13 microgram/ml at 4 hours of administration were maintained in plasma. The calculated plasma half-lives of sisomicin were 68.8 minutes in combination with cefotetan and 86.4 minutes alone. The urinary rcoveries of sisomicin were 79.3% and 76.1% in combination with cefotetan and alone, respectively, during 24 hours. There were no significant differences in the pharmacokinetics of sisomicin alone and in combination with cefotetan in dogs.
When guinea pigs received a single intramuscular injection of sisomicin (25 mg/kg) at week 8 of pregnancy, fetal sisomicin concentration at 2 h was highest in the kidneys, followed by the plasma and the cochlea; at 4 h it was not detected in the plasma or the cochlea. When dams were treated with 25 mg/kg during weeks 1-5 of pregnancy, fetal sisomicin concentration in the kidneys was 9 times greater than in the cochlea; in 3-week-old animals, a drug concentration of 4 microgram/g was detected only in the kidneys. When dams were treated during weeks 5-9 of pregnancy, the neonatal drug concentration was highest in the kidneys and the cochlea; no plasma concentration was detected. At 3 weeks of age, the concentration was highest in the kidneys and the cochlea. When lactating dams received sisomicin, only kidneys of suckling animals contained sisomicin at 0.4 microgram/g.
Hemoglobin and cytochrome P-450 have in common heme structure (i.e. protoporphyrin (IX), binding ability to molecular oxygen or carbon monoxide and enzyme-like activity (i.e. aniline hydroxylation; J.B.C. 251 3442, 1976). We have already reported the interactions between hemoglobin and several drugs, aminopyrine, aniline and steroid hormones, as determined from the spectral changes of hemoglobin. Similar results were obtained with many other drugs. Difference spectra of methemoglobin induced by most chemicals tested had a trough at 402 approximately 403 nm and a peak at 420 approximately 430 nm. Methanol and ethanol formed a peak at 403 nm and a trough at 420 nm. Difference spectra of oxyhemoglobin induced by most chemicals tested had a peak at 400 approximately 403 nm and a trough at 420 nm. Each of steroid hormones and amino acids tested induced a characteristic spectral change of methemoglobin or oxyhemoglobin. The effect of drug-administration on oxygen affinity of hemoglobin was then examined. We measured oxygen half saturation pressure (P50) using whole blood or purified hemoglobin. Addition of meclofenoxate HCl, PAS-Na and IHMS to purified hemoglobin solution increased P50. Whole blood samples, before and one hour after drug-administration, from 33 inpatients, 13 outpatients and 20 normal subjects (not on drug-administration) were used to determine delta P50 of 12 outpatients were within normal range (-0.5 approximately +0.5 mmHg). Those of 14 inpatients, however, were distributed out of range. The determination of delta P50 may be useful as a screening test for inappropriate drug-administration.
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