Controlled-release (CR) pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ) CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC) based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

AIM Malignant tumors of the larynx account for 2.3% of all malignancies, while their frequency among tumors of the head and neck ranges between 12% and 20%. Research on the general immune competence in patients with malignant diseases has provided useful insight in the relationship between immune disorders on one side and the clinical course on the other. Unfortunately, only few complete studies have been published so far with this regard in patients with malignant tumors of the larynx, and therefore our study was essentially aimed at establishing of general immunocompetence, presence and levels of the possible immune disorders and their association with the malignant tumors. MATERIAL AND METHOD The study included forty two patients with primary squamocellular laryngeal cancer. All the patients underwent surgery, out of whom fifteen were treated postoperatively with radiotherapy. We tested the immune competence prior to the operation and in the postoperative period nine months later. In the venous blood we examined T lymphocyte function, monocyte levels and mononuclear phagocyte function. RESULTS Preoperative evaluation of the presence and levels of general immune competence in patients with laryngeal cancer, showed a distinct decrease in the proliferative response to the PHA mitogen in vitro, with a tendency to normalize in patients who do not develop a relapse of the disease or distant metastasis during the follow-up period. During the whole study period, the number of monocytes and mononuclear phagocyte activity was above the normal level. CONCLUSION The patients with operable laryngeal carcinoma had considerable immune disorders at various levels, primarily at the level of T lymphocytes. Of all the disorders, reduced mitotic activity of T lymphocytes in response to mitogens showed the highest dependance on the presence of malignant tissue in the organism.