L~PLE~NTATION OF STERNATIONAL STANDARDS IN CLINICAL TRIALS IN RUSSIA V.K. Lepakhin, V. V. Chelt soy, V. Yu. S~it sarenk 9 , S. A. Udotova, A. G. Rudacov Russian Centre for Drug Expertise,Starovolynskaya, I0, I21358, Moscow, Russia.

A new drug may not be commercially marketed in Russia, unless it has been reviewed and approved as safe and effective by the State Regulatory Institutes. One of the most important part of the process of drag evaluation for registration is clinical trials. Drug regulatory authorities in Russia implemented rather strict requirements intol practice of clinical trials in Russia to harmonize Russian system with international standards. The initiation of clinical trials is possible only after State Pharmacological Committee permission. To get such a permission the sponsor of the drug has to submit general product information, quality certificate, acceptable scientific data, including the results of pro-clinical studies and so on. Clinical trials may be performed in accordance with the protocol in any state hospital of sponsor's own choice or following the recomenda- tions of the regulatory authoritie s. ~tudy proto- col has to be reviewed and approved by Ethics Committee. During the trial, monitoring by sponsor is possible, state inspection of clinical trials is done by random. After the completion of clini- cal trials the investigators prepare the final report and submit it to sponsor and regulatory authorities. Based on the results of the trials, Pharmacological Committee can recomend or not widespread medical application of the drug.

DRUG DISTRIBUTION IN CEREBROSPINAL FLUID (CSF) SYSTEM: PHYSIOLOGICAL AND CLINICAL IMPLICATIONS A. Vladi6, N. Strike6;' M. Klarica and M.Bulat Department of Pharmacology, Medical Faculty,. University of Zagreb, saiata i1, HR-1 Zagreb, Croatia

Distribution of drugs and endogenous substances in the CSF is poorly understood due to lack of an adequate experimental model. We have developed a new approach in dogs where substances can be applied into different compartments of CSF system (lateral ven- tricle, cisterna magna, cistema corporis callosi) in a short ether anesthesia. At different time intervals after that the samples of CSF can be obtained for anaiysis from cortical and lumbar CSF, lateral ventricle, cistema magna and cistema basalis. When 3H- benzylpenicillin (3H-BP) or 3H-inulin were applied into cisterna magna distribution of 3H-BP was extremely restricted to remote CSF compartments in comparison to 3H-inulin. However, when active transport of 3H-BP out of CSF was blocked by probenecid, distribution of both substances was similar. From analysis of our results we conclude: a) active transport restricts distribution of substances in CSF system, b) substances are carried along CSF system by pulsatory forward-backward mixing of CSF and not by unidirectional flow of CSF.

ACTIVITIES OF PHARMACOLOGISTS DURING DEFENSIVE WAR IN B O S N I A AND HERZEGOVINA (TOXICOLOGICAL ASPECT) Dubravka Potkonjak, S. Hukovic, Elvedina Kapic, Edin Omeragic University of Sarajevo, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology, Bosnia and Herzegovina.

There have been more than 500 attacks with militapy poisons and several folds more toxic fires in Bosnia and Herzegovina. One third of them has registered in Sarajevo. Pharmacologists helped in making diagnosis and therapy application. These toxic agents have been mostly irritants and caused more panic than the real damage of citizens. That have been poisons for temporarily inhibition with sensory eye and bronchial irritation by lacrimation and sneezing. Collaborators of Institute of Pharmacology have published just before to the war short text- book on symptomatology and therapy of potential mass poisoning caused by chemical toxic agents. When the war started pharmacologists have started with the project entitled "MASS THERAPY OF HEAVY POISONING CAUSED BY WAR POISONS AND WITH POISONS FOLLOWED WAR ACTIONS." I t has applicated acting research method, which: means that during the therapy the examinations of toxodynamic effects of these agents as well as scientific research have made, too. Apart from pharmacologists the leads of relevant clinics have collaborated in that project. Clinics have prepared for mass poisonings. Institute of Pharmacology has organized several scientific symposia on that subject. In conclusion it means that pharmacologists from Bosnia and Herzegovina used their pharmacological knowledge and/or experience for the defense of citizens and have not used their professional knowledge as war means. All pharmacological staff is in unchangeable during the whole war period.

CLINICAL PHARMACOLOGICAL ASPECTS OF WAR D R U G U T I L I Z A T I O N IN B O S N I A A N D HERZEGOVINA I. Zulic, N. Mulabegovic, A. Skrbo University of Sarajevo, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology, Bosnia and Herzegovina.

Before the war in Bosnia and Herzegovina it exists three faculties of medicine, one of pharmacy, one of dentistry and high nurse school. It has organized public health care with more than six thousands' physicians and pharmaceutical staff with about one thousand and half pharmacists. Many of those institutions have destroyed. Institute of pharmacology, clinical pharmacology and toxicology in Sarajevo with its staff has engaged from Ministry of health and University Clinical Center for more functions: - programming utilization of war stores of emergency drugs and other medical supplies; - making list of essential drugs; - making introduction for rational drug use or doctrinally therapy; - making information bulletin weekly; - cooperation with WHO office in Sarajevo; - installing phone computer information center for physicians, pharmacists and citizens; making pharmacological proposals or opinions for local pharmaceutical production; - leading state commissions for drugs and for poisons. All of that functions Institute is working three years already. We have had good cooperation with State Institute of drug control and with Faculty of Pharmacy. Naturally, we have had not normal conditions for work.

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