[Densitometric determination of piroxicam in plasma]. / Densitometrické stanovení piroxicamu v plazme.

Piroxicam was extracted from acid medium into chloroform and isolated on a thin layer of silica gel with the use of the system chloroform - absolute ethanol - benzene - aqueous ammonia (20:15:15:0.5). The intensity of fluorescence of stains was measured densitometrically (an Hg lamp, a filter FL - 39, 330 nm). The limit of detection of the stain is 0.020 microgram/ml of plasma.

Pharmacokinetics of flobufen and its main active metabolite in the rat.

Pharmacokinetic study of the anti-inflammatory [3H] flobufen (I) and its active metabolite (II) has been carried out in rats given po and iv doses of 2, 10, and 50 mg/kg I and equimolar doses of II. Various pharmacokinetic parameters of I and II [dose normalized AUC; mean residence time (MRT); systemic blood clearance; steady state volume of distribution, (Vss)] are dose-independent. I is completely absorbed from the gastrointestinal tract and is rapidly (MRT = 7.2 hr) converted to II, which is slowly (MRT = 2.6 days) eliminated from the blood. The fraction of total blood clearance that forms II is 0.83 following iv dose of I. The Vss of the less lipophilic metabolite II is somewhat lower (0.36-0.46 liters/kg) than that of the parent drug (0.51-0.56 liters/kg).

[Determination of sulbactam in human serum using capillary isotachophoresis]. / Stanovení sulbaktamu v lidském séru kapilární izotachoforézou.

A method of determination of sulbaktam in human serum by capillary isotachophoresis with the use of a conductivity detector was worked out. Prior to the proper analysis, a pretreatment of the sample of serum was carried out by extracting sulbaktam to butyl acetate. The total yield of the proposed analytical procedure with an extraction first stage approaches 94%. The smallest determinable amount of the sample corresponds to 1 micrograms of sulbaktam in 1 ml of serum. The reported method was employed to evaluate the samples of sera of volunteers after intravenous administration of the dosage form sulbaktam-ampicillin (VUFB) and the foreign pharmaceutical preparation Unasyn (Pfizer). Statistically insignificant differences in pharmacokinetic parameters have confirmed that the preparations are highly bio-equivalent.

Interleukin-2 activated cells from peripheral blood of patients with systemic lupus erythematosus.

The effect of recombinant interleukin-2 (IL-2) on proliferative and cytotoxic response of peripheral blood mononuclear cells (PBMC) was investigated in a group of 21 patients with systemic lupus erythematosus (SLE). There was a significant decrease in thymidine uptake of peripheral blood mononuclear cells when compared with controls. However, IL-2 induced cytotoxicity was not diminished and minimal frequencies of lymphokine-activated killer (LAK) cells precursors remained in the range of control group. These data provide an evidence about the dissection between proliferative and cytotoxic response of PBMCs to exogenous interleukin-2 in patients with SLE in vitro. The factors contributing to this effect and the clinical significance of these findings remains to be answered.

Clinical trials of anti-osteoarthritic agents.

Two long-term studies of chondroprotective agents in the treatment of osteoarthritis (OA) have been the subject of considerable interest. The studies included large numbers of patients with OA of the hip and of the knee followed for ten and five years. A range of criteria were chosen as parameters for monitoring the progression of disease, and statistical analysis of the results showed that GP-C modified positively the progression of OA. In view of the large number of criteria assessed, and the complexity of the results, it was decided that a reevaluation of the gonarthritis study would be appropriate using a range of indices in the statistical analysis. The statistical re-analysis of data confirmed that long-term treatment with GP-C positively modifies the progression of OA.

Pharmacokinetics and pharmacodynamics of conventional and controlled-release formulations of metipranolol in man.

The pharmacokinetics and beta-adrenoceptor blocking effects of conventional and sustained-release metipranolol have been studied in 6 healthy male volunteers given a single oral dose of 40 mg. Plasma drug concentrations determined by TLC and a radioreceptor assay, and the inhibition of exercise-induced tachycardia, were monitored for 48 h. Relevant amounts of active metabolites other than deacetylmetipranolol were not found. Compared to conventionally formulated metipranolol, the controlled-release product had a prolonged mean residence time (10.7 vs 5.5 h), the peak drug concentration was halved and the time to peak drug concentrations was delayed. Relatively constant plasma concentrations (cideal = 6.5 ng/ml) and a clinically significant reduction of exercise-induced tachycardia were maintained throughout a 24 h dosing interval. An individual deacetylmetipranolol plasma concentration-effect relationship was evaluated using the Emax model. Mean parameters were Emax 26% and C50 2.9 ng/ml.

Interspecies pharmacokinetic scaling of metazosin, a novel alpha-adrenergic antagonist.

Based on pharmacokinetic data from mice, rats, and rabbits, the prediction of pharmacokinetics of intravenous metazosin in man has been performed. The correlations were based upon allometric scaling of plasma clearance and the volume of distribution at steady-state. A one-compartment body model approximating clinical pharmacokinetics fits well the elimination phase of subsequently measured metazosin concentrations in volunteers. Fitting human pharmacokinetic data to allometric equations enabled us to superimpose pharmacokinetic curves from different species.

[Various clinical courses of hypersensitivity vasculitis with eosinophilia]. / Rozdílné klinické prubéhy hypersenzitivních vaskulitid s eozinofilií.

The authors present three case-histories of patients who were followed up for prolonged periods and where the diagnosis of hypersensitive vasculitis was made. During the follow up period it was not possible to prove development into a different group of vasculitis or to detect a hitherto latent associated disease. Another common sign of the investigated patients was eosinophilia repeatedly found in peripheral blood, bone marrow and tissues. According to clinical criteria the above patients could not be included in groups of known types of vasculitis which are associated with eosinophilia. The patients differed significantly as to clinical manifestations of the disease, the response to different therapeutic approaches and some laboratory immunological indicators. The authors discuss the possible participation of eosinophilia in the tissue damage.

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.