Titre du document / Document title

PK-PD modelling of the effect of cefaclor on four different bacterial strains

Auteur(s) / Author(s)

DE LA PENA Amparo ⁽¹⁾ ; GRÄBE Annemarie ⁽¹⁾ ; RAND Kenneth H. ⁽²⁾ ; REHAK Edelgard ⁽³⁾ ; GROSS Jens ⁽³⁾ ; THYROFF-FRIESINGER Ursula ⁽³⁾ ; MÜLLER Markus ^{(1 4)} ; DERENDORF Hartmut ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmaceutics, College of Pharmacy, University of Florida, P.O. Box 100494, Gainesville, FL 32610-0494, ETATS-UNIS
⁽²⁾ Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, P.O. Box 100275, Gainesville, FL 32610-0275, ETATS-UNIS
⁽³⁾ HEXAL AG, Industriestrasse 25, Holzkirchen 83607, ALLEMAGNE
⁽⁴⁾ Department of Clinical Pharmacology, Vienna University Medical School, Vienna, AUTRICHE

Résumé / Abstract

The effect of cefaclor against relevant bacterial strains was studied by employing a combined in vivo pharmacokinetic (PK)-in vitro pharmacodynamic (PD) approach. For this purpose selected isolates of Escherichia coli, Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae were exposed in vitro to the interstitial cefaclor profile obtained in vivo in the interstitial space fluid of human tissue after administration of commonly used doses of cefaclor and the change in the number of colony forming units per millilitre (CFU/ml) versus time was monitored. Fitting of the data using a modified E_max-model resulted in a set of mean pharmacodynamic parameters (k₀, k_max, EC₅₀) for each bacterial strain. The parameters derived from these experiments were used in a computer-simulation of the antibacterial effects for different dosing regimens and formulations of cefaclor, notably an immediate (IR) and a modified (MR) release formulation. Dosage regimens were compared using the ratio between the number of bacteria remaining after 24 h of a given treatment (N_24h). The results indicate that the number of bacteria of all investigated strains killed per day is equivalent when the same daily dose is administered twice a day with the MR dosage form than when given three times a day with the IR dosage form, in spite of the fact that the MR dosage form has approximately 20% lower bioavailability. Best results were obtained with the three-times a day regimen of the MR formulation. In conclusion, the present in vivo-PK/in vitro-PD simulations of the antimicrobial effects of cefaclor indicate that a twice-daily treatment with a MR formulation may offer a convenient and safe alternative to the conventional tid treatment.

Revue / Journal Title

International journal of antimicrobial agents   ISSN 0924-8579 

Source / Source

2004, vol. 23, n^o3, pp. 218-225 [8 page(s) (article)] (12 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1992) (Revue)

Mots-clés anglais / English Keywords

Dosage form ; β-Lactams ; Cephalosporin derivatives ; In vitro ; Dose ; Application method ; Sensitivity resistance ; Pharmacokinetic pharmacodynamic relationship ; Antibiotic ; Antibacterial agent ; Controlled release form ; Immediate release form ; Biological activity ; Pharmacokinetics ; Bacteria ; Cefaclor ; Minimum inhibitory concentration ;

Mots-clés français / French Keywords

Forme pharmaceutique ; β-Lactamines ; Céphalosporine dérivé ; In vitro ; Dose ; Modalité traitement ; Sensibilité résistance ; Relation pharmacocinétique pharmacodynamie ; Antibiotique ; Antibactérien ; Forme libération contrôlée ; Forme libération immédiate ; Activité biologique ; Pharmacocinétique ; Bactérie ; Céfaclor ; Concentration minimale inhibitrice ;

Mots-clés espagnols / Spanish Keywords

Forma farmacéutica ; β-Lactams ; Cefalosporina derivado ; In vitro ; Dosis ; Modalidad tratamiento ; Sensibilidad resistencia ; Relación farmacocinética farmacodinamia ; Antibiótico ; Antibacteriano ; Forma liberación controlada ; Forma liberación inmediata ; Actividad biológica ; Farmacocinética ; Bacteria ; Cefaclor ; Concentración mínima inhibidora ;

Mots-clés d'auteur / Author Keywords

Cephaclor ; Pharmacokinetic ; Pharmacodynamic ; Immediate release ; Modified release ;

Localisation / Location

INIST-CNRS, Cote INIST : 22211, 35400011669554.0030