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Biomedical subjects

D R Uges

Publications and source records attributed to D R Uges.

84 records · Page 5Linked to original sources
PubMed1983

Determination of the antitumor agent SOAz (1,3,3,5,5 pentakis(aziridino)-1 lambda 6,2,4,6,3 lambda 5, 5 lambda 5 thia-triazadiphosphorine-1-oxide) by a gas chromatographic assay suitable for pharmacokinetic studies in man.

A sensitive method, based on capillary gas chromatography using a thermionic detector, has been developed for the new antitumor agent pentakis(aziridino)-thiatriazadiphosphorine-oxide, (NPAz2)2NSOAz ('SOAz'), in order to obtain pharmacokinetic data from patients receiving this drug IV in clinical trials. A structural analog of SOAz, (NPAz2)2NSOPh ('SOPh'), was used as an internal standard. The detection limit of SOAz with this method was 0.01 mg/l for serum and 0.04 mg/l for urine. The coefficient of variation (n = 10) was 6,0% at 1.5 mg/l in serum and 1.6% at 75.0 mg/l in urine. Analytical recoveries averaged 89.9% from serum and 86.7% from urine. In two patients treated with subtoxic doses of SOAz (55 mg/m2), serum levels were found ranging from 3.0 to 0.16 mg/l at 10 min and 12 h, respectively, after administration. This assay seems to be useful for determining SOAz in samples from patients receiving subtoxic doses of SOAz.

Aged↗
PubMed1983

Clinical pharmacokinetics of (NPAz2)2NSOAz: 'SOAz'.

Pharmacokinetic studies of 1,3,3,5,5 pentakis (aziridino)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5 thiatriazadiphosphorine-1-oxide ('SOAz'), a new antineoplastic agent containing an inorganic ring system and five aziridino groups, were performed in six patients who took part in a phase I clinical trial of the agent. The drug was administered as a rapid IV infusion. Serum decay curves could be fitted to an open two-compartment model of drug disappearance. After a short initial phase with a t 1/2 (+/- SD) of 7.8 +/- 4.2 min a terminal phase with a dose-independent half-life of 203 +/- 17 min occurred. The coefficient of apparent distribution was 0.71 +/- 0.13. The renal clearance was 75 +/- 11 ml/min and the total body clearance 162 +/- 23 ml/min. A percentage of 46.5 +/- 6.6 of the administered drug could be recovered unchanged in the urine within 24 h. It is concluded that in view of concentrations known to be effective in vitro, administration in large single doses may be advantageous. Dose adjustments should be made for patients with impaired renal function.

Adult↗
PubMed1982

4-Aminopyridine kinetics.

Nine healthy subjects (7 men; 2 women) received single 20-mg IV injections of 4-aminopyridine (4-AP). Six of the subjects received the same dose in the form of enteric-coated tablets and four the same dose in uncoated tablets; treatments were at least 2 wk apart. Blood, saliva, and urine were assayed for 4-AP using a high-performance liquid chromatography. Kinetic analysis of serum concentrations after intravenous dosing resulted in the best fitting of a triexponential model in five and a biexponential model in four subjects. The apparent volume of distribution (V) was 2.6 +/- 0.9 (mean +/- SD) 1 kg-1, the terminal half-life (t 1/2) 3.6 +/- 0.9 hr, and the total serum clearance 0.61 +/- 0.14 1 hr-1 kg-1. Saliva concentrations were higher than those in serum after 5 min, with a mean correlation coefficient of 0.989 (n = 5). The t 1/2 and V calculated from serum and saliva concentrations were of the same order. The total urinary excretion of unchanged 4-AP was 90.6 +/- 7.8% after intravenous doses and 88.5 +/- 4.8% after oral doses of enteric-coated tablets. The bioavailability of the enteric-coated tablets calculated from the area under the serum concentration curve (95 +/- 29%) did not differ from that calculated from urinary excretion (98 +/- 8%). Protein binding of 4-AP was found to be negligible. Biotransformation is unlikely.

4-Aminopyridine↗
PubMed1982

Influence of oral atropine or hyoscine on the absorption of oral diazepam.

The influence of oral atropine or hyoscine on the absorption of oral diazepam administered at the same time was studied in eight volunteers using a three-way crossover randomized double-blind design. No difference was found in the timing of sedation or in the degree of sedation after diazepam alone or in combination with the anticholinergics. Diazepam serum concentrations were not significantly different after the three regimens. It is concluded that the anticholinergics can be given with diazepam for oral premedication without interfering with diazepam absorption.

Administration, Oral↗
PubMed1981

Liquid-chromatographic determination of 4-aminopyridine in serum, saliva, and urine.

We have developed "high-performance" liquid-chromatographic methods for determining 4-aminopyridine, an acetylcholine-releasing drug, in serum, saliva, and urine. As little as 1 microgram/L can be detected by extracting the alkalinized sample plus the internal standard (3,4-diaminopyridine) into dichloromethane, mixing the organic phase with 1-pentanol, evaporating the dichloromethane, and injecting the residue onto a reversed-phase column, where it is eluted with acetonitrile/methanol/aqueous ammonium carbonate, with detection at 245 nm. Analytical recoveries from serum averaged 86.7%. The CV at 50 micrograms/L was 2.9% (n = 8). For urine samples containing very high concentrations of 4-aminopyridine, we mixed urine and potassium carbonate in an automatic injector vial, extracted the drug into dichloromethane, centrifuged, and injected an aliquot of the extract into the chromatograph. Analytical recoveries averaged 92%, and the CV was about 2% for drug concentrations of 0.1-8 mg/L of urine.

4-Aminopyridine↗
PubMedDate not supplied

Electrochemical and surface characterization of a nickel-titanium alloy.

For clinical implantation purposes of shape memory metals the nearly equiatomic nickel-titanium (NiTi) alloy is generally used. In this study, the corrosion properties and surface characteristics of this alloy were investigated and compared with two reference controls, AISI 316 LVM stainless steel and Ti6A14V. The anodic polarization curves, performed in Hanks' solution at 37 degrees C, demonstrated a passive behaviour for the NiTi alloy. A more pronounced difference between the corrosion and breakdown potential, i.e. a better resistance to chemical breakdown of passivity was found for the NiTi alloy compared to AISI 316 LVM. X-ray electron spectroscopy (XPS) and scanning electron microscopy (SEM) were undertaken to study the elemental composition and structure of the surface films prior to, and after immersion in Hanks' solution. The passive film on the NiTi alloy consists of a mainly TiO2-based oxide with minimal amounts of nickel in the outermost surface layers. After immersion in Hanks' solution the growth of a calcium-phosphate layer was observed. The passive diffusion of nickel from the NiTi alloy, measured by atomic absorption spectrophotometry reduced significantly in time from an initial release rate of 14.5 x 10(-7) microg cm(-2) s(-1) to a nickel release that could not detect anymore after 10 days. It is suggested that the good corrosion properties of the NiTi alloy and the related promising biological response, as reported in literature, may be ascribed to the presence of mainly a TiO2-based surface layer and its specific properties, including the formation of a calcium-phosphate layer after exposure to a bioenvironment.

Alloys↗
PubMedDate not supplied

Effects of c-myc oncogene modulation on drug resistance in human small cell lung carcinoma cell lines.

Small cell lung carcinoma (SCLC) is characterized by rapid development of resistance to drugs, such as cisdiamminedichloroplatinum (II) (cDDP) and anthracyclines. The molecular basis for resistance to cDDP and adriamycin (Adr) is poorly understood. One of the genetic alterations observed in SCLC, which is correlated with poor prognosis, is amplification and overexpression of c-myc oncogene. Therefore, activation of the c-myc oncogene might form a basis for resistance. The relationship between c-myc and cDDP as well as Adr resistance was analyzed by down-regulation of endogenously expressed c-myc in the human SCLC cell line GLC4, and its cDDP and Adr resistant sublines (GLC4-cDDP and GLC4-Adr). Cells were incubated with an unmodified antisense (AS) oligodeoxynucleotide complementary to the first 5 codons of the c-myc mRNA in serum free culture medium. Pre-incubation with 15 microM AS c-myc, reduced c-myc protein expression and induced 30-35% growth inhibition in all 3 cell lines. It resulted in increased cDDP sensitivity in GLC4-cDDP but not in GLC4. However, this pre-incubation did not affect Adr sensitivity in all lines. The effect of AS c-myc pretreatment on cDDP resistance was not mediated by changes in cell cycle distribution. These findings suggest that c-myc plays a role in cDDP resistance by effects other than those on cell cycle distribution.

Antibiotics, Antineoplastic↗