It was attmpted to figure out a formula which expresses the relation between concentration of an antimicrobial agent injected intramuscularly and time after injection, presuming that the body consists of one or two homogeneous compartments and that the agent is absorbed and eliminated after the principle of first order reaction. The following formula was resulted.
C=A/β-α (e^-at-e^-βt)
The serum concentration of the agent (C) is expressed as a function of time after injection (t). A pattern of a curve described by the formula is determined by rate constant of elimination (α), rate constant of absorption (β) and a constant (A) relating to injected dose and size of distribution space.Those constants are specific for a different kind of agents. This theoretical curve has a good fit with actual data-points determined by bioassay.
The details of the method for calculating a nonlinear regression of data-points and for estimating rate constants of absorption and elimination were mentioned. The formula thus obtained was found useful for estimating total clearance, renal clearance and half-life.

View full abstract

Following intravenous injection of sodium colistin methane sulfonate (CL-M) in male rabbits, the 24 hours urinary and biliary recovery of CL-M was examined by bioassay.
Further 24 hours urinary and biliary metabolite of CL-M and that recovery was examined by TLC, NRP, and column chromatography.
The results obtained were as follows.
1) CL-M was excreted about 75% in the urine and slightly in the bile within 24 hours after administration.
2) As metabolite, colistin-N-glucuronide was found on the average of 1. 7% in the urine and 6. 7% in the bile, respectively, within 24 hours after administration.

View full abstract

Effects of cytosine arabinoside on culture cell line KU-1, which was derived from human transitional cell carcinoma of the urinary bladder, were evaluated. The cell growth was remarkably inhibited by cytosine arabinoside at concentration of 1. 0, 10. 0 and 100. 0, μg/ml in this system, which was almost equal effect of Thio-Tepa in the same condition in vitro, however, the cytocidal action was not stronger than that of the latter.
On the other hand, time lapse studies of microscopic cinematography on these experiments observed complete detachment of cell sheet from glass surface in 10 days following interruption of cell activity without shrinkage of cell sheet by 1. 0, μg/ml of cytosine arabinoside, while in 14 days recovery of growth was observed from temporally collapsed cell sheet exposed by Thio-Tepa at same dosis.
The results conclude that a specific inhibition effect of cytosine arabinoside on culture cell line KU-1, derived from human bladder carcinoma was suspected.

View full abstract

The in vitro antibacterial activity of mafenide acetate was studied and the following results were obtained.
1. Antibacterial activity of mafenide acetate was found not to be influenced by the medium used for the test, being a conspicuous difference from other sulfonamide drugs.
2. Antibacterial spectrum of mafenide acetate was quite similar to that of homosulfamine, markedly susceptible species among tested being Staph. aureus, Staph. epidermidis, Strept. pyogenes, Strept. pneumoniae and Clost. tetani of gram-positive bacteria, and Pseud. aeruginosa of gram-negative bacteria.
3. Among the clinical isolate of 283 strains from 13 species tested, Staph. aureus, Strept. pyogenes and Pseud. aeruginosa were particularly susceptible to mafenide acetate, the degree of action being less than those observed with gentamicin and fradiomycin though.
4. The cross-sesistance to mafenide acetate was not observed on the sulfadiazine-resistant strains on the sulfadiazine-resistant strains of Pseud. aeruginosa, while it was observed on the gentamicin and sulfadiazine-resistant strains of Prot. inconstans and fradiomycin and sulfadiazine-resistant strains of Prot. rettgeri.
5. The in vitro development of resistance to mafenide acetate was studied on Staph. aureus and Pseud. aeruginosa by 10 passages, and no significant increased resistance was observed.
6. The effect of mafenide acetate on the growth curve of Staph. aureus and Pseud. aeruginosa was studied, and it was found that the bacterial growth inhibition was observed immediately after addition of mafenide acetate, even in lower concentration than sulfadiazine, and the bactericidal action was also shown, particularly in high concentration.

View full abstract

The synergic actions of CBPC, SBPC and PL-B were observed on Pseudomonas aeruginosa No. 12 by-Chequer board titration method.
In either case of the combination of CBPC with PL-B, SBPC with PL-B, the simultaneous administration showed the highest bactericidal effect, followed by the case of addition of PL-B after adding CBPC or SBPC, while the reverse case showed the similar effect to that of each drug alone.
The therapeutic experiment of infection demonstrated that the combination of SBPC with PL-B showed., superior effects to those of each drug alone. In comparison to this, the combination of SBPC with PL-B revealed more favorable effect by the simultaneous administration in 2 hours after infection.

View full abstract

Oral administration of a mold protease, Onoprose SA before intramuscular administration of penicillin G, aminobenzyl penicillin or cefazolin to rats. significantly increased the concentrations of these antibiotics in the bronchial wash. Other proteases. such as Bromelin and Serratia peptidase had similar effects. The effect of Onoprose SA was greater in rats with fat embolism in the lungs than in normal rats.
These results indicate that Onoprose SA stimulates the appearance of antibiotics in normal and diseased respiratory tracts and alveoli.

View full abstract

In order to compare the curative effect and side effect of cephradine (CED) with those of amoxicillin (AMPC), comparative clinical experiments have been carried out by means of a double blind method upon 195 patients of pneumonia in 28 institutions throughout the country. CED was administered orally for 2 weeks at a daily dose of 2 g, and AMPC was administered similarly at a daily dose of 1 g. Both subjective and objective symptoms were observed in detail and various examinations were also performed. The clinical effectiveness was judged by a doctor in charge as well as by committee members composed of several doctors. This committee interpreted the chest X-ray films of all cases following a certain standard, and judgement of severity and effectiveness was made on every case individually before opening the key code. On the contrary, the numerical judgements of severity and clinical effectiveness were made on the base of individual symptoms and examination data. When the key code was opened, comparison was made on the homogeneity of background factors of the patients as well as aeverity in both groups of drug administration, and the clinical effectiveness and side effect were determined statistically.
Among 195 cases of drug administration (92 cases of CED and 103 cases of AMPC), 12 cases were excluded because of the following reasons-5 cases : different schedule of administration, 5 cases : pulmonary tuberculosis, one case : lung cancer and pleurisy, one case : atelectasis after bronchography. No significance was observed between the two treatment groups regarding the background except age groups of male. Clinical effectiveness judged by doctors in charge was excellent 20 : 23 (CED : AMPC, respectively), good 43 : 53, fair 11 : 5, poor 7 : 9, aggravated 1 : 3, evaluation impossible 5 : 3, thus showing no significance between the two groups. Side effects were seen in 16 cases of CED (5 cases : symptoms, 12 cases : laboratory abnormalities) and 20 cases of AMPC (7 cases : symptoms, 13 cases : laboratory abnormalities). Drug administration was discontinued in 4 cases of AMPC due to the side effect, but in none of CED. No significance was seen between the two groups either on the side effect or on the utility.
The committee members excluded 33 cases of CED and 27 cases of AMPC to strictly compare the drug effectiveness on pneumonia. In the adopted 59 cases of CED and 76 cases of AMPC, no singificance was observed on the backgrounds except age groups of male. Clinical effectiveness judged by committee members was excellent 4 : 5, good 38 : 50, fair 4 : 12, poor 13 : 9, and showed no significance. No significance was observed on the clinical effectiveness by numerical judgement either.
Regarding the degree of improvement in CRP, the group of AMPC was better than that of CED, and the latter was better than the former regarding the degree of improvement in volume of sputum. No significance was observed in the two groups as for improvement of symptoms

View full abstract