Drug effects in clinical chemistry  (on original Miro's drawing)

The role of Pharmacokinetics / Pharmacodynamic (PK/PD) information in the clinical development of antibiotics: A Scientific/Regulatory Workshop  A workshop co-sponsored by  ISAP and MPA / EMEA (Swedish Medical Product Agency, Uppsala, Sweden [MPA] / Committee for Propriety Medicinal Products of the European Agency for the Evaluation of Medicinal Products EMEA, London, UK)    June 9th-10th, 1999, Wiks Castle, Sweden (near Uppsala)  Goals and Objectives - Organization - Programme  Attending the meeting - Venue - Accomodation  Useful links - Credits

    The meeting should serve to construct the scientific basis for Proposals to be presented by the European Working Party (EWP) of the Committee for Proprietary Medicinal Products (CPMP) to the European Agency for the Evaluation of Medicinal Products (EMEA) for considering the development of a 'Guidelines for the choice of dose and dosing regimens based on pharamcokinetic and pharmacodynamic data in relation to outcome and the development of resistance'.

Introduction

    There us now convincing evidence that the dose, dosing interval and clinical efficacy of an antibacterial can be related to various pharmacokinetic (PK) and pharmacodynamic (PD) parameters.  Similarly, PK and PD data can be used to assist in a rational approach to setting breakpoints between susceptible and resistant bacteria (currently, many national bodies differ in their approach and different breakpoints exist in the vaious countries of the European Union [EU]).

    Evidence to hand suggest that the ratio of area-under-the-serum-concentration-time-curve to the MIC is the predictor of efficacy for fluoroquinolones; for beta-lactams, the parameter is the time the serum concentration exceeds the MIC, and for aminoglycosides the ratio of C_max to MIC is relevant to outcome.  Recent information inidates that attention to proper dosing can minimize the mergence of resistance.

    Application for Maketing Authorization for new antimicrobials agenst should provide PD and PK data relevant to the agent and the indications (i.e. the sites of infection) sought.  A more rational approach to the selection, design and interpretation of these studies has the potential to provide a firm base for the latter phase of clinical development and, particularly, for the conduct of the major trials of clinical safety and efficacy.  Such data would also serve as the basis for a more scientific selection of the preliminary susceptibility test breakpoints to be taken forward into Phase III.

Aims

    To provide guidance to the Pharmaceutical Industry on:

• the scope of human pharmacokinetics pertinent to the antibacterials;
• the scope of pharmacodynamic investigations for differing classes of antimicrobials for both in vitro and in vivo models of infection;
• the appropriate design of clinical trials to validate PK/PD that has been determined in pre-clinical studies;
• to develop appropriate PK/PD data to minimize the development of bacterial resistance, and more specifically:
• to select a preliminary beakpoint between susceptible and resistant populations of bacteria based on PK and PD data;
• to confirm the validity of that breakpoint from clinical trial experience.

    As a national drug agency within the European Union (EU), the Swedish Medical Product Agency (MPA; in Swedish: Läkemedelsverket) has been rapporteur for the adopted guidelines on antimicrobials.  When the Committe Medicinal Products (CPMP) recently adopted a point to consider document on PK/PD relationships for antibiotics (see Goals and Objectives), partly based on an initiative of ISAP (presented by Prof. R. Wise, ISAP member), MPA was again apponted as rapporteur, with the Netherlands, UK and Germany as co-rapporteurs.  CPMP reffered this task to the ad-hoc European Working Party (EWP).

    The present workshop is therefore organized by MPA in conjunction with ISAP to bring scientific imput from academia as well as from high level regulatory authorities, with special reference to recent EMEA initiative in the area of public health and antibiotic resistance. 

Organizers:

• ISAP: O. Cars (Upsala, Sweden)
• MPA/CPMP/EWP: B. Odlind (Uppsala, Sweden)

For the time being, the organizers do not intend to make the meeting public.  Its announcement is therefore only for information purposes.  Should this situation change, ISAP members will immediately be notified by a special issue of the ISAP electronic Newsletter. Non-ISAP members are invited to examine this WEB page at regular intervals for additional information when available. 

Wiks Castle, Sweden (about 35 km from Stockholm Arlanda Airport and close to Uppsala).  Details (maps and driving directions) will be made available if the meeting is opened to the public). 

No accomodation will be provided nor will ISAP or MPA be handling hotel reservations.

	Home page of ISAP		Uppsala and some of its university buildings
	European Agency for the Evaluation of Medicinal Products (EMEA)		Linne botanical garden
	Swedish Medical Products Agency (MPA - Läkemedelsverket)		Uppsala Gustavianum (17th century anatomical theater)
	General information and Accomodation in Uppsala		Male choir of Uppsala

• ISAP Web site and ISAP diffusion list are kindly and generously housed on the INTERNET Server of the Faculty of Medicine of the 'Université Catholique de Louvain' in Brussels, Belgium, with the expert help of Benoît Debande, MD.  All comments and queries should however be sent exclusively to the ISAP Webmaster.
• Drug effects in Clinical Chemistry: on original Miro's drawing from this book edited by Nils Tryding, Christer Tufvesson and Oswald Sonntag, ( ISBN 91-85574-38-4 ISSN 0282-5783, Pp. 551 and 364) and published in Stockholm 1996 by the National Corporation of Swedish Pharmacias, Pharmasoft and Swedish Society for Clinical Chemistry.  This image is taken from Nils Tryding Web site <http://home.swipnet.se/~w-12360/#Drug effects>
• other images are from the WEB sites to which they are linked.