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Biomedical subjects

Z Trnavská

Publications and source records attributed to Z Trnavská.

At least 19 recordsLinked to original sources
PubMed1990

Theophylline protein binding.

The binding of theophylline to human serum albumin and human plasma has been studied by equilibrium dialysis at 22 degrees C, pH 7.4. The binding data were analyzed according to the Scatchard model. The values of binding parameters obtained for human serum albumin (N1 = 1.8, K1 = 2.6 x 10(3) l/mol; N2 = 6.0, K2 = 7 x 10(2) l/mol) were quite similar to those obtained for human plasma (N1 = 1.8, K1 = 2.7 x 10(3) l/mol; N2 = 5.0, K2 = 8.6 x 10(2) l/mol). It is suggested that theophylline interacts with the albumin fraction in human plasma proteins. The percentage of theophylline protein binding was determined in serum from patients with asthmatic diseases and from healthy volunteers. pH of serum samples was adjusted to 7.4 just before dialysis. The mean of theophylline binding in patients was slightly but significantly higher (37.5 +/- 0.4%) than those found for healthy volunteers (35.5 +/- 0.3%). The intersubject variability of theophylline binding was relatively small in both groups due to the standardization of experimental conditions.

Adolescent↗
PubMed1989

[Pharmacokinetics and chronotherapy of delayed action theophylline (Euphyllin CR)].

Monitoring of theophyllinaemia in the course of 24 h during treatment with theophylline anhydrate capsules (Euphyllin CR) was used in 20 children (9-15 years) and in 20 adults (18-61 years) with bronchial asthma. The doses used in children were 5.96 mg/kg at 7 a.m. and 10.2 mg/kg at 7 p.m., while in adults the morning and evening doses were similar (4.35 and 4.89 mg/kg). After the first dose in the morning the serum theophylline concentration (STC) did not differ in children and adults (10.4 and 10.5 mg/l). In adults the half-time of absorption was twice as high as in children (0.63 and 0.3 h), as well as the time when the peak theophylline concentration was reached (2.7 and 1.39 h). In children a double dose of the drug at night ensured a STC of 11.2 mg/l and a maximum theophyllinaemia (C max = 13.5 mg/l between 8 p.m. and 6 a.m. (measured by the EMIT method). In adults the values during the night were significantly lower than in day-time (STC: ANOVA test P less than 0.05, C max: T-test P less than 0.01). The percentage fluctuation in individual subjects was small (36-49) interindividual, fluctuations in children and adults were considerable (105 to 207). From the chronoprofile of the pharmacokinetics of Euphyllin CR ensues that at the age of 9-15 years the most important indicators are similar to those in adults and that both groups should be given at night a double dose, as compared with that administered in the morning.

Adolescent↗
PubMed1989

Pharmacokinetics of once-daily theophylline dose following the morning versus evening administration.

The pharmacokinetics of theophylline (Uniphyllin) in blood and saliva was compared after morning and evening administration of a once-daily dose in a randomized cross-over study. Ten bronchial asthma patients received multiple doses of 800 mg theophylline at 8 a.m. and 8 p.m. under controlled food conditions. The precision of the serum concentration prediction from salivary measurements in individual patients was sufficient to obtain identical pharmacokinetic parameters and parallel concentration-time curves. There were no significant differences in the values of mean residence time and area under the concentration-time curves after morning and evening dosing, either in the kinetics of elimination and in the volume of distribution. The fluctuation of concentrations during the dosing intervals was 100% after morning doses and 80% after evening doses. No consistent interference with food was found. Circadian variation in the kinetics of drug disposition after once-daily theophylline administration did not occur. In order to achieve higher therapeutical levels at night and in the morning, the evening dosing seems to be preferable.

Adult↗
PubMed1987

Comparative pharmacokinetic analysis of theophylline in serum and saliva.

The kinetics of theophylline disposition in serum and saliva was evaluated after single and multiple circadian administration of a sustained-release theophylline formulation (Euphyllin CR) to 20 asthmatic children. Salivary concentrations were proportional to serum drug levels, with the significant correlation of r = 0.92. The kinetics of theophylline absorption and elimination and the mean residence time were identical in both saliva and serum estimations. In steady-state conditions after multiple drug administration, the area under the concentration-time curve and the magnitude of peak levels in saliva were reduced proportionally with decreased serum theophylline concentrations. The significantly higher volume of theophylline distribution in saliva confirmed that salivary concentrations represent the free, pharmacologically active fraction in plasma. The determination of theophylline salivary levels could therefore be of clinical importance. The values of the saliva/serum ratio determined in the elimination phase of concentration-time curves for individual patients were constant and stable over the treatment period of three weeks. Saliva appears to be a convenient and noninvasive alternative to blood for the assessment of the variable pharmacokinetic parameters of theophylline and for around-the-clock monitoring of individual dosage regimens, especially in paediatric patients.

Adolescent↗
PubMed1985

The effect of cimetidine on the pharmacokinetics of salicylic acid.

The pharmacokinetics of the interaction between salicylic acid and cimetidine was investigated in 11 healthy male and female volunteers. The plasma concentrations of total and free salicylic acid were measured. The kinetic disposition of salicylic acid after multiple administration of cimetidine (1 g per day) showed two modifications: the elimination rate was slower and plasma clearance was reduced. The corresponding area under concentration-time curves was always significantly greater. These differences were the same in both sexes. The rate of absorption, peak salicylate concentration and plasma protein binding of salicylic acid in the presence of cimetidine were not changed.

Adult↗
PubMed1984

Plasma protein binding and interaction studies with piroxicam.

The binding of non-steroidal antirheumatic drug piroxicam to human serum albumin, human plasma and serum has been studied by equilibrium dialysis at 22 degrees C, pH 7.4. The binding data were analyzed according to Scatchard model. The values of binding parameters obtained for human serum albumin are quite similar to those obtained for human plasma and serum (N1 = 0.3, K1 = 3.0 x 10(5) l/mol; N2 = 7, K2 = 3.5 x 10(3) l/mol). We suggest that piroxicam interacts with the albumin fraction in human plasma proteins. The displacement of piroxicam (in the therapeutical concentration of 4.5 x 10(5) mol/l) from the binding to human serum albumin and human plasma has been studied. The concentration of albumin and albumin fraction in plasma was 2.9 x 10(-4) mol/l. The displacement substances were drugs--diazepam, warfarin and salicylic acid, and endogenous substances-bilirubin and palmitic acid. Only in the presence of salicylic acid in high clinical concentration (14.5 x 10(-4) mol/l) and palmitic acid in the molar ratio to albumin 5:1, free piroxicam substantially increased, which may be of clinical significance. Other studied substances displaced piroxicam only in high concentrations exceeding the therapeutical and physiological range. The evidence was found for the similarity of piroxicam and warfarin high-affinity binding site.

Anti-Inflammatory Agents↗
PubMed1984

Binding of piroxicam to synovial fluid and plasma proteins in patients with rheumatoid arthritis.

The protein binding of piroxicam in synovial fluid and plasma from patients with rheumatoid arthritis was studied in vitro by equilibrium dialysis. The binding parameters were calculated from the experimental data with the Scatchard model, assuming binding to two classes of sites. Each plasma sample was diluted to an albumin concentration equal to that of synovial fluid from the same patient. The association constants for primary and secondary binding sites in the concentration range of piroxicam 4.5-90 X 10(-5) mol/l were similar in synovial fluid and in plasma. For synovial fluid K1 = 2.38 X 10(5) l/mol and K2 = 2.29 X 10(3) l/mol; for plasma K1 = 1.93 X 10(5) l/mol and K2 = 2.08 X 10(3) l/mol. The number of binding sites was also the same in the two fluids. Although the concentration of piroxicam in synovial fluid was about half that in plasma, the binding of piroxicam to protein in synovial fluid was the same as in plasma.

Anti-Inflammatory Agents↗
PubMed1983

Sex differences in the pharmacokinetics of salicylates.

The kinetics of disposition of total and free salicylic acid (SA) in blood plasma was evaluated after single and multiple oral administration of acetylsalicylic acid (ASA) to healthy female and male volunteers. In both single and multiple dose studies significant sex differences were found in the plasma levels of SA, which were due, at least in part, to individual, sex-determined differences in the rate of absorption and elimination of SA; a slower absorption rate in men reduced the magnitude of the peak plasma levels of SA. The corresponding area under concentration-time curves were always significantly lower. The elimination rate of SA in men was increased in comparison with women. The higher plasma clearance in men resulted from the kinetics of absorption and elimination. The sex differences appear to be clinical significance, since men achieved lower plasma levels of SA than women after the same weight-adjusted dose of ASA.

Adult↗
PubMed1983

Binding of indomethacin ester with tropic acid to human serum albumin.

The binding affinities of the ester of indomethacin with tropic acid and of indomethacin to human serum albumin were studied using the method of equilibrium dialysis. The binding constants were calculated from the experimental data by the Scatchard model. Binding to human serum albumin (14 X 10(-5) mol/l) was significantly lower for esterified indomethacin than for nonesterified. The tropic ester of indomethacin has an association constant for the primary binding sites of 2.16 X 10(5) l/mol, and while the association constant for indomethacin is 8.15 X 10(5) l/mol. The differences found between the binding affinities of the ester of indomethacin and of indomethacin may contribute to the different pharmacokinetics of these drugs.

Humans↗
PubMed1980

Characterization of salicylate binding to synovial fluid and plasma protein in patients with rheumatoid arthritis.

Protein binding of salicylate in synovial fluid and plasma from patients with rheumatoid arthritis was studied by equilibrium dialysis. Protein binding in the synovial fluid was considerably lower at all salicylate concentrations studied (0.07 - 2.2 mM). Scatchard plots of the data were analyzed assuming binding to two classes of binding sites, each plasma sample being diluted to an albumin concentration equal to that in synovial fluid from the same patient. Binding to the primary binding sites was considerably decreased in synovial fluid in comparison with plasma. The affinity of the secondary binding sites was slightly lower. Thus, at a low therapeutic drug concentration, the decreased binding of salicylate to synovial fluid protein in patients with rheumatoid arthritis could mainly be accounted for by decreasing affinity of binding to the primary binding sites.

Arthritis, Rheumatoid↗
PubMed1979

The binding of colchicine and its derivatives to bovine and human serum albumin and human plasma.

The protein binding of colchicine and its derivatives demecolcine and desacetylcolchiceine was studied by equilibrium dialysis at 22 degrees C and pH 7.38 in bovine and human serum albumin and human plasma. Colchicine and demecolcine (2 X 10(-4) -5 X 10(-4) mol/l) is not bound to proteins. The binding of desacetylcholchiceine was 60--80% in the range 10(-4)-5 X 10(-4) mol/l. The association constant for a single binding site was 8.03 X 10(3) 1/mol for human serum albumin and 13.20 X 10(3) 1/mol for human plasma. The binding profiles for desacetylcholchiceine were quite similar in human serum albumin (4% conc.) and human plasma (3.8% conc. of albumin fraction). We suggest that desacetylcolchiceine was likely to be bound predominantly to albumin. Salicylic acid in vitro, at clinical concentrations (1.8--14.5 X 10(-4) mol/l), significantly decreases the binding of desacetylcolchiceine to human serum albumin.

Animals↗