Comparative pharmacokinetics of two oral bezafibrate preparations.

The pharmacokinetics of two oral solid preparations of bezafibrate, available in the Spanish market, was studied. Both preparations were tablets, an immediate-release formulation (A) and the other a slow-formulation (C). We selected a crossover design, and twelve healthy male volunteers participated in the study. Using a sensitive HPLC method, plasma concentrations of bezafibrate were monitored over a period of 12 h. after administration of treatment A and 24 h. for treatment C. In treatment A, two tablets were administered at an interval of six hours. The maximum plasma concentration (Cmax), time to Cmax(tmax) and area under curve (AUC infinity o), in the two doses of treatment A, were compared by analysis of variance and found to be significantly different between the two doses. The relative bioavailability based on (C: 1st-Dose-A) ratio of AUC infinity o was within the range 100 +/- 20%.

Dissolution kinetics of bezafibrate in two solid forms for oral administration.

The dissolution kinetics of two solid and oral formulations of bezafibrate have been studied. These preparations are available in the Spanish market. Both of them are tablets, one conventional-release (A) and the other slow-release formulation (C). Dissolution studies have been performed using the system proposed by the USP XXI. The solubility of the drug was determined in each release medium at 37 degrees C. The results indicate that the sink conditions were not satisfied. The evaluation of the dissolution rate-kinetics is performed by three different mathematical approaches. Strong differences in its "in vitro" behaviour were found.

In vitro evaluation of the dissolution rate of crystalline suspensions destined to intramuscular administration.

The aqueous suspensions for intramuscular administration belong to the group of the dosage forms, that have a sustained release behaviour. These are based on the low aqueous solubility of the administered molecule whose aqueous suspensions form a depot in the muscular tissue which controls the absorption. The assays performed previously with two molecules of these characteristics have shown the inability of the habitual methods used for evaluating the dissolution rate of a drug, to determine the possible behaviour of these drugs in a definite and concrete formulation. For this reason, we have designed and developed a new method which allows us to support future processes, such as agglomeration and, possibly, cyst forming, that could be developed "in vivo". In this way, a more reliable prediction of the efficiency of inefficiency of this kind of formulation will be possible. Tha validity of our system has been studied with three formulations. Two of them were sustained release cefazolin molecules showing agglomeration problems "in vivo" and the other one a commercial penicillin-G benzathine commercial with a great efficacy demonstrated in habitual clinical practice.

Pharmacokinetic study of etodolac after rectal administration; "in vitro" release kinetics.

The present study describes the pharmacokinetic behaviour of a new dosage form of etodolac not available in the Spanish market: suppositories. Rectal administration was chosen as an alternative for the oral route. The dose used was 200 mg. The pharmacokinetic parameters of the drug are estimated by means of two possible methods i.e., model-independent and model-dependent. The results obtained are compared and discussed. At the same time, an "in vitro" study of the release kinetics of etodolac from the suppository was performed using a continuous flow system without fluid recirculation or accumulating reservoir. The dissolution media used were buffered aqueous solutions at pH 6.5 and 7.4. The results obtained show that the release of the drug from the supposity could be a limiting factor for its absorption.

Pharmacokinetics of cefroxadine after infusion to healthy volunteers.

The pharmacokinetics of cefroxadine in healthy human volunteers was studied in plasma and urine, after an infusion administration of 1 g of this drug for 0.5 h. Blood and urine samples were microbiologically quantified by diffusion on solid gelose using Bacillus Subtilis ATCC 6633 as the test organism. Plasma and urine profiles were fitted to a reduced two-compartment model not having inactivating biotransformation as a route of elimination. The parameters of distribution for this model show a rapid disposition (t1/2 alpha = 0.28 h) and an average volume of the central compartment of 0.15 +/- 0.04 l/kg (range 0.20-0.09). The dominant terminal half-life (beta-phase) was 1.17 +/- 0.26 h (range 0.90-1.67). The total body volume 0.41 +/- 0.09 l/kg (range 0.30-0.52) indicates that there is no diffusion of the antibiotic into intracellular fluids of poorly perfused tissues due to its high elimination rate.

Dissolution rate and in situ intestinal absorption kinetics of guanyl-cysteine.

The study of the dissolution behaviour of guanyl-cysteine is presented. The drug was assayed as a pure non-formulated product and formulated in hard gelatine capsules. Aqueous solutions buffered at different pH were used as dissolution fluids. The dissolution rate constant of the drug in this formulation was estimated. Our results show that dissolution of guanyl-cysteine occurs very rapidly. As pH of the dissolution fluid increases, the rate constant slightly decreases. The study of the absorption kinetics of guanyl-cysteine from small intestine of rats was performed with the experimental technique proposed by Doluisio. Six different concentrations of the drug were assayed for the estimation of the absorption rate constant of guanyl-cysteine under our experimental conditions. Our results show that intestinal absorption of the drug occurs as a first-order process.

Pharmacokinetic study of vincamine teprosilate.

The results obtained by the authors in the pharmacokinetic study of vincamine teprosilate after oral and i.v. administration to young healthy volunteers and after oral administration to patients aged 68 to 84 years are presented. The description of the assay for each administration route is reported in the protocol. Plasma levels of vincamine teprosilate were assayed by reverse phase HPLC with spectrofluorimetric detection. The data obtained after i.v. administration made it possible to define the pharmacokinetic model and to estimate parameters. Concentration-time data were adapted to a biocompartmental open model with alpha value of 2.9080 and beta value 0.1047. In oral administration, the overlapping of the fast disposition phase and the absorption phase led to an apparent monocompartmental fit; in both young and aged volunteers, the absorption rate constants as well as the elimination rate constants were calculated. In both groups no significant differences in tmax values were found and no latency period was noticed . Cmax values were similar in both groups of patients; the lower distribution volume in aged volunteers compared to younger ones contributed to this finding. Differences in absorption rate constants in aged and young volunteers (0.53 h-1 and 0.73 h-1 respectively) are analysed. Vincamine teprosilate bioavailability after oral administration was found to be 20 +/- 5%. Possible vincamine teprosilate dose dependence kinetics are suggested.