Abstract
Proper documentation of new antimicrobial drugs for governmental registration authorities includes extensive pharmacokinetic studies. Pharmacokinetics represents the bridge between the in vitro and in vivo phases of drug development. Both healthy human volunteers and patients must be studied, the former during the initial stages of the pharmacokinetic studies. The documentation should give information on the following: absorption from the gastrointestinal tract, bioavailability, pharmacokinetic model, impact of increasing doses (oral and intravenous), metabolism, routes and degree of elimination, interaction with food and other drugs, impact of the steady state, and serum protein binding. Basic pharmacokinetic parameters used are the serum half-life, clearance, distribution volume and dose dependence. The bioavailability of oral doses must be determined using the same dose sizes and subjects. Data on extravascular penetration should also be included in complete documentation. Key diseases in which the pharmacokinetics should be studied are reduced renal and liver function, heart failure, pregnancy, cystic fibrosis and intestinal diseases. The consequences of low age (e.g. newborns) and old age also require some attention.
Similar content being viewed by others
References
Josefsson K, Bergan T, Magni L: Dose-related pharmacokinetics after oral administration of a new formulation of erythromycin base. British Journal of Clinical Pharmacology 1982, 13: 685–691.
Wagner JG: Fundamentals of pharmacokinetics. Drug Intelligence, Hamilton, IL, 1975.
Bergan T: Overview of acylureidopenicillin pharmacokinetics. Scandinavian Journal of Infectious Diseases 1981, Supplement 29: 33–48.
Stoeckel K, Macnamara PJ, Brandt R, Plozza-Nottebrock H, Ziegler WH: Effect of concentration dependent plasma protein binding on pharmacokinetics on ceftriaxone pharmacokinetics. Clinical Pharmacology and Therapeutics 1983, 23: 650–656.
Sjövall J: Tissue levels after administration of bacampicillin, a prodrug of ampicillin, and comparison with other aminopenicillins: a review. Journal of Antimicrobial Chemotherapy 1981, 8, Supplement C: 41–58.
Nord CE, Heimdahl A, Kager L, Malmborg AS: The impact of different antimicrobial agents on the normal gastrointestinal microflora of humans. Review of Infectious Diseases 1984, Supplement 1: 270–275.
Bergan T, Örtengren B, Westerlund D: Clinical pharmacokinetics of co-trimazine. Clinical Pharmacokinetics 1986, 17: 97–103.
Colburn WA, di Santo AR, Gibaldi M: Pharmacokinetics of erythromycin on repetitive dosing. Journal of Clinical Pharmacology 1977, 17: 592–600.
Bergan T, Solberg R: Assay of cefotaxime by high-pressure liquid chromatography. Chemotherapy 1981, 27: 155–165.
Rohwedder R, Bergan T, Thorsteinsson SB: Trans-intestinal elimination of ciprofloxacin. Chemotherapy 1990, 36: 77–84.
Bergan T, Lolekha S, Cheong MK, Poh CL, Patancharoen S: Consequences of diarrhoeal disease on the pharmacokinetics of norfloxacin. Scandinavian Journal of Infectious Diseases 1988, Supplement 56: 11–13.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bergan, T. Requirements for the documentation of pharmacokinetic properties of antimicrobial agents. Eur. J. Clin. Microbiol. Infect. Dis. 9, 506–509 (1990). https://doi.org/10.1007/BF01964292
Issue Date:
DOI: https://doi.org/10.1007/BF01964292