Effect of caffeine on quinidine transport to the central nervous system in rats.

We studied the effect of caffeine on the transport of quinidine through the blood-brain barrier (BBB) to the central nervous system (CNS) in rats. The anesthetized animals received quinidine in the form of a retrograde intra-arterial bolus injection (15 s) into the right axillary artery 30 min after receiving a subcutaneous injection of caffeine (test group) or physiological solution (control group). Rats were decapitated at 30, 60, 90, 120, and 240 s after quinidine administration. Blood samples were taken from the left jugular vein. Upon washing, the brain, was divided into the brainstem, cerebellum, and cerebral hemispheres to determine the quinidine content in each section, using a standard spectrofluorimetric method. Quninidine attained maximal concentrations in the CNS with a latency compared with that in blood; the CNS values were higher. Quinidine kinetics showed two compartments in the CNS, one consisting of the brainstem and cerebellum, in which quinidine concentrations were higher, and the other the cerebral hemispheres. Caffeine caused a significant deceleration of quinidine transition through the BBB to the CNS.

[Professional and social responsibilities of clinical pharmacology]. / Profesionalna i drustvena odgovornost klinicke farmakologije.

According to the decision of the Scientific and educational board of the Medical Faculty in Novi Sad the Institute for pharmacology toxicology and clinical pharmacology introduced the clinical pharmacology in 1975. Postgraduate studies were organized for those wishing to specialize, i.e. to get their M.Sc. degree in clinical pharmacology. Besides the youngest members of the Institute (now they are all associate professors) these studies were successfully completed by many doctors from other clinics or those employed in pharmaceutical industry. The publications which the Institute published from the field of pediatric clinical pharmacology were the very first ones not only in our country but also in world proportions. International methods for the evaluation (DDD, ATC code) of the scope and structure of drugs usage were introduced and modified according to our conditions and requirements. The studies on the usage of drugs were among the first pharmacoepidemiological studies in country and abroad. On the basis of these activities the Institute was two times the organizer of the scientific meeting sponsored by WHO. As a response to a sudden increase of the need for information on drugs due to disturbed supply and distribution of drugs from abroad (through humanitarian aid) a telephone and modem information service has been organized within the Institute. The printing of the book titled Drugs in Use was initiated (five editions since 1992) together with the issues on computer discs. The publishing of the journal Pharmaca Iugoslavica was also started under the auspices of the Association of Health Care Organizations. The service for adverse events registration was also organized. Through its activities in planning and organization of pharmacokinetic and clinical investigations, development of new analytic methods and performance of pharmacokinetic studies the Institute contributed to the development of new drugs and gave new theoretical solutions in pharmacokinetics. The Institute also initiated the establishment of the Committee for drugs of the Medical Faculty. Its professors are members of the Commission for Social Insurance, Federal Commission for Drugs and Federal Commission for Poisons. Through all mentioned activities the Institute has greatly influenced not only our but also general medical community.

Effect of the aluminium ion on hepatic elimination of quinine and quinidine.

A study of the influence of the aluminum ion on the blood and hepatic kinetics of two alkaloid stereoisomers--quinine and quinidine--after their p.o. and s.c. administration (80 mg/kg) to rats was carried out. It appeared that the mode of application of the stereoisomers had different effects on their resorbtion in control animals. In the case of s.c. application, blood concentrations of quinine in some time intervals reached significantly higher levels than those found for quinidine. Hepatic elimination of quinine appeared to be independent of the mode of its application, whereas the elimination of quinidine was significantly increased after its s.c. application. Pretreatment of rats with aluminium chloride (600 mg/kg, i.p.) 2 h before injecting one of the stereoisomers had a different effect on their concentrations in blood, and significantly higher effect on their bile elimination. The quinine concentrations in blood after its p.o. administration were not changed significantly, but after s.c. application these concentrations were increased in some time intervals. The presence of the aluminum ion caused a significant increase in the rate of hepatic elimination of quinine, whereas it had no significant effect on quinidine elimination.

[Medicines and lactation]. / Lekovi i dojenje.

The factors that determine the transfer of medicine from mothernal blood to breast milk are the relative molecular mass of the substance, liposolubility, plasma half-life, binding to plasma proteins, pKa, the rate of metabolism and the dose taken by the breast feeding mother. The transfer of large number of medicines is small, so that the amount reaching the infant is negligible. But, certain drugs pass the milk into quantities sufficient to cause adrverse effects and these drugs should be avoided during breast-feeding. Having these facts in mind, the physician is in most cases in the position to select an appropriate medicine compatibile with breast-feeding.

[The value of local administration of antibiotics in treatment of bone infections]. / Vrednost lokalne primene antibiotika u lecenju infekcije kosti.

An open, controlled, randomized clinical investigation was carried out in 33 patients suffering from osteomyelitis. In the first group, 17 patients, a through drainage with sterile physiologic solution was applied, while in the second group, 16 patients, antibiotic was added to the sterile physiologic solution. In all patients values of C reactive protein (CRP) in the blood were examined, and later on every third day after the operation. A significant difference of average values of CRP between the 3rd and 21st day in both groups of patients was established, as well as the similarity in average values of CRP, which points to the fact that the mechanical effect of through drainage is dominant, speaking about rinsing focus of infection and eliminating necrotic tissues and small sequesters.

The effect of aluminium chloride upon the transition of drugs through the blood-brain barrier into the central nervous system.

In order to determine the effect of Al3+ upon the transition of drugs through the blood-brain barrier into the central nervous system we examined its effect upon a drug that dissociates as a cation (quinidine) and drugs that dissociate as anions (acetylsalicylic acid and pentobarbital). The entry and exit of quinidine into and out of the brain in mice pre-treated with AlCl3 was inhibited. Al3+ did not compete with acetylsalicylic acid for the penetration through the blood-brain barrier but did slow down its elimination from the brain. Brain kinetics of the examined drugs showed good correlation with their central pharmacodynamic effects.