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Biomedical subjects

T Oguma

Publications and source records attributed to T Oguma.

85 records · Page 5Linked to original sources

[The prophylactic effects of latamoxef against the postoperative infections to open heart surgery. Studies on the penetration of latamoxef into the pericardial fluid and the auricle of heart].

Latamoxef (LMOX, Siomarin) at a dose of 2 g was intravenously administered to each of 23 patients undergoing the open heart surgery and the concentrations in serum, pericardial fluid and auricle of heart were measured. Pharmacokinetic observations are summarized below. The peak serum concentration (t = 0) was 227.3 micrograms/ml and the serum half-life (T1/2 beta) was 1.74 hours. In pericardial fluid, LMOX reached the peak concentration of 28.44 micrograms/ml at 4.9 hours and the half-life was 9.99 hours. In auricle of heart, LMOX reached the peak concentration of 42.78 micrograms/g at 6.9 minutes and the half-life was 1.74 hours. It was shown that LMOX penetrates well into the pericardial fluid and the auricle of heart, and it is considered that their levels exceed the minimal inhibitory concentration against a majority of clinical isolates except Pseudomonas aeruginosa.

Adolescent↗

Distraction rod instrumentation with posterolateral fusion in isthmic spondylolisthesis. 53 cases followed for 18-89 months.

Fifty-three cases of isthmic spondylolisthesis were treated with distraction rod instrumentation and posterolateral fusion with or without nerve root decompression, and they were followed for an average of 39 months. Thirty-one cases without neurologic deficit were treated with instrumentation and fusion only. In 22 cases of predominant sciatic pain with neurologic deficit signs, nerve root decompression and instrumentation with fusion were conducted. The results showed a 90.6% solid union rate with satisfactory clinical improvement. Realignment of the vertebral displacement such as reduction of olisthesis and widening of the olisthetic disc spaces was obtained to some extent. No serious complications were encountered.

Adolescent↗

[Transfer of latamoxef into human burn blister fluid and its pharmacokinetic analysis].

Latamoxef (LMOX) (50 mg/kg) was administrated intravenously to burned patients over 1 hour period. Burn blister fluid and serum were taken during 8 hours after injection, and concentrations of LMOX in burn blister fluid and serum were determined by bioassay using E. coli as a test organism. The serum concentrations of LMOX were 170.8 +/- 30.6 micrograms/ml at 30 minutes, 227.0 +/- 19.8 micrograms/ml at 1 hour, 90.3 +/- 21.4 micrograms/ml at 2 hours, 52.9 +/- 14.6 micrograms/ml at 3 hours, 38.7 +/- 13.3 micrograms/ml at 4 hours, 25.1 +/- 8.1 micrograms/ml at 5 hours, 20.5 +/- 8.1 micrograms/ml at 6 hours, 13.0 +/- 5.5 micrograms/ml (mean +/- S.D., n = 5) at 8 hours after the injection. The LMOX concentrations in burn blister fluid were 36.9 +/- 32.8 micrograms/ml at 30 minutes, 77.5 +/- 42.2 micrograms/ml at 1 hour, 85.4 +/- 19.6 micrograms/ml at 2 hours, 76.4 +/- 18.5 micrograms/ml at 3 hours, 63.5 +/- 17.8 micrograms/ml at 4 hours, 54.9 +/- 17.1 micrograms/ml at 5 hours, 34.8 +/- 10.3 micrograms/ml at 6 hours, 25.2 +/- 4.8 micrograms/ml (mean +/- S.D., n = 7) at 8 hours after the injection. The data obtained were analysed pharmacokinetically. The serum levels were analysed by two-compartment model, and the LMOX levels in burn blister fluid were analysed by the model, in which blister was considered as a small part of the peripheral compartment. In results, Tmax and Cmax of LMOX levels in burn blister fluid were calculated as 1.81 hours and 90.6 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Posterolateral fusion with instrumentation in the symptomatic failed back patients.

Thirty-two symptomatic failed back patients after lumbar spine surgery performed for disc lesions underwent posterolateral fusion involving an adaptation of two distraction rod or combined distraction and compression rod instrumentation following decompression procedure when necessary. The main causative pathology of persistent pain was segmental instability with or without nerve root entrapment. The average follow-up period was 35 months. Twenty-eight patients responded that they were satisfied with the final operation. Fusion rate was 100% at the present study. The salvage instrumentation surgery to the failed back was thought to have brought about removal of instability, restoration of the disc height to some extent and decompression in some cases.

Adult↗

Acute effect of ethanol on hepatic first-pass elimination of propoxyphene in rats.

The purpose of this investigation was to determine if ethanol enhances the acute toxicity of propoxyphene not only by its central nervous system depressant effect but also by inhibiting the otherwise pronounced presystemic biotransformation of the analgesic. Administration of propoxyphene to adult male rats by injection into either the systemic (jugular vein) or hepatic portal circulation (pyloric vein) revealed that 40 +/- 12% (mean +/- S.D.) of a 12 mg/kg dose reached the systemic circulation intact after injection of the drug into the portal circulation. This estimate, based on the area under the plasma concentration time curve, was confirmed by the relative amounts of propoxyphene excreted unchanged in the urine. Acute infusions of ethanol, 1.5 ml/kg/hr from -3 to 0 hr and 0.5 ml/kg/hr from 0 to +3 hr into the portal circulation, increased the total systemic clearance of propoxyphene from 64 to 95 ml/min/kg on the average (P less than .02), probably due to increased hepatic blood perfusion rate. The same rate and route of ethanol administration caused an increase in the average systemic availability of propoxyphene from 28 to 56% (P less than .001) after injection of 8 mg/kg into the portal circulation. Since orally administered propoxyphene is ordinarily subject to extensive presystemic biotransformation in humans, the frequent association of ethanol intake with fatal propoxyphene intoxication may be due, at least in part, to an increased systemic availability of propoxyphene when taken with ethanol.

Animals↗

A novel pharmacokinetic method for analysis of placental transfer of latamoxef in humans.

A novel pharmacokinetic method was developed for analysing the behaviour of a drug in tissues. The absolute transfer ratio of a drug to a tissue was defined using the pharmacokinetic parameters obtained by this method. Composite data of latamoxef (moxalactam) concentration in maternal blood, umbilical cord blood and amniotic fluid following a 2g intravenous injection to pregnant women at delivery were analysed by this method to study the drug behaviour in pregnant women, fetuses and amniotic fluid. Latamoxef kinetics in pregnant women at full term were generally similar to that in previously reported healthy subjects. The concentration of latamoxef in umbilical cord blood peaked about 2 hours after dosing then decreased in parallel with the maternal blood concentration. The amniotic fluid concentration peaked about 7 hours after administration, then decreased slowly. The absolute transfer ratios to fetus and amniotic fluid were calculated to be about 2.5 and 0.37% respectively.

Amniotic Fluid↗

Pharmacokinetic correlation between experimental and clinical effects on human non-small cell lung cancers of cis-diammineglycolatoplatinum (254-S) and cis-diamminedichloroplatinum.

We attempted to correlate the in vitro and in vivo antitumor activities of cis-diammineglycolatoplatinum (254-S), a novel platinum complex, and cis-diamminedichloro-platinum (CDDP) against the established culture cell lines and xenografts of human non-small cell lung cancer (NSCLC) with their clinical effects, based on the previous finding that the cytotoxicity of CDDP depends on the area under the curve (AUC). The concentration of 254-S and CDDP inhibiting the in vitro growth of 4 cultured NSCLC lines by 50% (IC50) was 0.82-7.8 and 0.53-4.2 micrograms/ml, respectively, showing a similar level. Of the 4 cell lines, only the most sensitive line, RERF-LC-AI, showed an IC50 close to a specific concentration (0.50 for 254-S and 0.32 micrograms/ml for CDDP) that reproduces in vitro the clinical AUCfree (24.8 and 5.34 micrograms-hr/ml) of the respective drugs. We treated 6 lines of human NSCLC xenografts implanted in nude mice with 254-S and CDDP at a particular dose (13.2 and 3.7 mg/kg) that is equivalent to the clinical doses with respect to the plasma AUCfree. 254-S and CDDP exhibited significant antitumor effects on 2 and 1 of the 6 lines, respectively. These in vitro and in vivo findings were considered to be relatively well correlated with the reported clinical response rates of 15-19% for 254-S and 14-15% for CDDP.

Adenocarcinoma↗

Pharmacokinetics of platinum in cancer patients following intravenous infusion of cis-diammine(glycolato)platinum, 254-S.

The pharmacokinetics of platinum in cancer patients were examined following an intravenous infusion of cis-diammine(glycolato) platinum, 254-S. The plasma concentrations of total platinum, which decreased biexponentially after the infusion, were proportional to the dose over the range of 10 to 120 mg/m2, suggesting linearity of the pharmacokinetics. The plasma concentrations of ultrafilterable platinum were similar to those of total platinum and there was little difference in the pharmacokinetic parameters between total platinum and ultrafilterable platinum. These findings show that almost all of the platinum derivative is unbound, which is thought to be the active form, in plasma after administration of 254-S. Platinum was eliminated from blood faster when given as 254-S rather than as cisplatin because of the low protein binding. The urinary recovery within 24 hours was about half of the dose, suggesting that platinum given as 254-S was distributed to various tissues and organs in an active form.

Adolescent↗