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Biomedical subjects

Y Tan

Publications and source records attributed to Y Tan.

At least 217 records · Page 12Linked to original sources
PubMed1986

Pharmacokinetics of naproxen at two dosage regimens in healthy volunteers.

The pharmacokinetic differences between two dosage regimens of naproxen (1000 mg once daily vs 500 mg twice daily) were studied at steady-state in seven healthy male volunteers. The twice daily regimen resulted in statistically significant higher trough serum levels, larger AUC0----24; also the time span with a concentration over 50 micrograms/ml was longer. The urinary excretion of naproxen metabolites was slightly greater upon once daily dosing. The VDextrap and, to a lesser extent the total body clearance, were larger upon the once daily regimen with a longer t1/2 beta as a consequence. As yet one can only speculate about the therapeutic implications of these findings.

Adult↗
PubMed1985

Determination of sulfinpyrazone and four metabolites in plasma and urine by high pressure liquid chromatography.

An HPLC method for the simultaneous determination of sulfinpyrazone and its p-hydroxy, sulfone, sulfide and p-hydroxysulfide metabolites in human plasma and urine samples was developed. Optimization with regard to sample preparation and chromatographic conditions was investigated. In the final procedure samples were acidified with HCl, extracted with a 1 + 1 (vol/vol) mixture of 1-chlorobutane and chloroform; urine extracts were re-extracted with citrate buffer (pH 4.5). HPLC was performed on reversed phase (RP 8) columns with a 48 + 52 (vol/vol) mixture of ethanol and citrate buffer (pH 2.5) as the mobile phase. The lower limit of detection for sulfinpyrazone and the sulfide metabolite is 10 ng/ml, for the other metabolites it is 50 ng/ml. An example of application of this procedure to pharmacokinetic studies in a volunteer receiving a single oral dose of sulfinpyrazone is given.

Chromatography, High Pressure Liquid↗
PubMed1985

Effects of indomethacin and sulindac on hydrochlorothiazide kinetics.

We investigated the influence of two nonsteroidal anti-inflammatory drugs, indomethacin and sulindac, on the diuretic effect and kinetics of hydrochlorothiazide in healthy subjects. In an open, randomized, crossover study, eight healthy subjects were treated with hydrochlorothiazide, 50 mg a day, for 4 weeks. In the second and fourth weeks, indomethacin, 25 mg three times a day, or sulindac, 200 mg twice a day, were added. Blood pressure, body weight, plasma levels of potassium, creatinine, and albumin, the hematocrit, plasma renin activity (PRA), and the 24-hour urinary excretion of sodium and potassium were measured at the end of each week. Plasma concentrations of hydrochlorothiazide and its urinary excretion were also determined 0.5, 1, 2, 3, 4, 8, 10, and 24 hours after HCTZ dosing. When indomethacin was added to hydrochlorothiazide, body weight and plasma potassium levels increased and PRA decreased. Hydrochlorothiazide kinetics were not influenced. In contrast, sulindac decreased the renal clearance of hydrochlorothiazide and increased hydrochlorothiazide plasma levels in two subjects who had somewhat lower endogenous creatinine clearance values than the other subjects. Except for a decrease in PRA, there were no dynamic interactions. Our results suggest that an interaction between indomethacin and hydrochlorothiazide is caused by dynamic mechanisms such as inhibition of renal prostaglandin synthesis, whereas sulindac may alter the renal clearance of hydrochlorothiazide.

Adult↗
PubMed1983

Furosemide kinetics and dynamics in aged patients.

Furosemide (F) is frequently used by elderly persons. We wanted to know whether age-related changes in the disposition or the effect of F occurred and whether these changes could be predicted or explained. Kinetics and diuretic effects were studied after intravenous F injection in geriatric patients (70 to 93 yr of age). The changes in kinetics were as follows: slightly enlarged volume of distribution (0.16 +/- 0.04 l) inversely related to serum albumin, diminished total body clearance (73 +/- 27 ml/min), decreased renal clearance (40 +/- 18 ml/min), and prolonged elimination t1/2 (180 +/- 87 min). F effects were unchanged only if the decreased renal delivery of F and the decreased glomerular filtration rate were taken into account. Renal F clearance correlated best with endogenous creatinine clearance (ECC) and with F effects. Only ECC and plasma creatinine turned out to be useful patient characteristics to predict all F effects. Many drugs have an increased effect in elderly persons if a standard dose is used, based on the attainment of higher free plasma levels. In the case of F, however, the effects are decreased because they depend on decreased glomerular filtration of electrolytes and water and on decreased renal F secretion. These decreases are in part age dependent and in part disease dependent.

Adult↗
PubMed1982

Specimen handling and high-performance liquid chromatographic determination of furosemide.

A simple high-performance liquid chromatographic method to measure furosemide in plasma and urine is described. Furosemide fluoresces best, but is unstable, at acidic pH and is subject to photochemical degradation. These factors were analysed and the results prompted changes in previously described methods. All specimens were very carefully protected from light; extraction and acidification were done with acetic acid instead of hydrochloric acid. With these precautions no 4-chloro-5-sulphamoylanthranilic acid was found in biological specimens. The main metabolite was furosemide glucuronide (20% of furosemide excretion). Sensitivity was 0.1 and 0.5 microgram/ml for plasma and urine, respectively. The applicability of our method for furosemide studies is demonstrated.

Adult↗
PubMed1982

Pharmacokinetic and pharmacodynamic studies of tienilic acid in healthy volunteers.

A simple and reliable HPLC method for the determination of tienilic acid ((TA) Selacryn, Selcryn, Diflurex, Ticrynafen) and its alcoholic metabolite in plasma and urine has been developed. In 8 healthy adult volunteers the plasma and urinary levels of tienilic acid and its alcoholic metabolite, and plasma and urinary levels of sodium, creatinine and uric acid were measured after oral administration of tienilic acid 250 mg. The pharmacokinetic parameters found differed only slightly from those reported in the literature, as there was faster absorption and a shorter half-life. TA is probably excreted by a saturable renal tubular transport mechanism. The pharmacodynamic effects of tienilic acid developed quickly, the uricosuric effect being very impressive and the natriuretic effect moderate. These effects disappeared in about 8 h. An inverse relationship was found between the starting plasma uric acid level in an individual and the maximal uric acid clearance - the higher the plasma uric acid level, the lower was the maximum effect. Plasma tienilic acid level and natriuretic effect were correlative within individuals and intra-individually (p less than 0.05). Urinary tienilic acid level and natriuretic effect were correlated, too (p less than 0.05 to p less than 0.001), but only intraindividually. No correlation between drug level and uricosuric effect was found.

Adult↗
PubMed1982

Aspirin-induced asthma in children.

Aspirin-sensitive asthma is not well documented in children. It may present as a triad of (1) allergic rhinitis, (2) nasal polyps and/or sinusitis and (3) bronchial asthma precipitated by aspirin. Four cases in children are presented. The pathophysiology probably involves the biosynthesis of prostaglandins.

Acetylation↗
PubMedDate not supplied

Preliminary crystallization studies of calmodulin-dependent protein phosphatase (calcineurin) from bovine brain.

Calcineurin is a serine/threonine protein phosphatase which catalyzes the hydrolysis of both phosphoseryl/phosphothreonyl and phosphotyrosyl proteins as well as low molecular weight compounds such as p-nitrophenyl phosphate. It is a hetero-dimeric protein consisting of a 60 kDa A chain and 19 kDa B chain. Calcineurin A is organized into functionally distinct domains such as a catalytic domain, a calcineurin B binding domain, a calmodulin-binding domain, and an inhibitory domain. Calcineurin B has four EF-hand calcium binding domains with a secondary structure that is homologous to calmodulin but its metal binding properties are more similar to troponin-C. The N-terminal myristoyl group of calcineurin B might play a role in the interaction between subunits A and B during phosphorylation/dephosphorylation processes. Crystals of size 0.125 x 0.07 x 0.03 mm and 0.7 x 0.03 x 0.02 mm have been obtained for calcineurin and the A subunit respectively. Crystals of calcineurin show strong diffraction to 5.3 A and weak diffraction to 3.0 A on rotating anode operated at 50 kV and 100 mA. Further work is in progress to improve the X-ray diffraction quality of these crystals and to obtain well diffracting crystals of calcineurin B.

Animals↗
PubMedDate not supplied

IL-2 gene therapy of advanced lung cancer patients.

We report here Phase I clinical-trial studies of retroviral-mediated interleukin-2 (IL-2) gene transfer to tumor-infiltrating lymphocytes that are re-infused to advanced lung cancer patients with pleural effusions. Ten lung cancer patients with malignant pleural effusions for whom all conventional therapy had failed were included in this Phase I protocol. Tumor infiltrating lymphocytes (TIL) from the patients were exposed to the retroviral plasmid pL(IL-2)SN containing the human IL-2 gene. Approximately 1-6 x 10(10) TIL cells transfected with IL-2 were re-infused into the chest cavity of each patient. The toxicity of this treatment with TIL/IL-2 gene therapy in these patients was minimal with transient slight fever of approximately 37.5. Pleural effusions did not re-accumulate for at least 4 weeks in six of ten patients. One patient was observed to have not only the resolution of the pleural effusions, but in addition the size of the original tumor decreased as seen by CT. The clinical results indicate this method of cancer gene therapy is safe and possibly efficacious against pleural effusions due to advanced lung cancer.

Adenocarcinoma↗