Poster at ECCMID 2008:
K.S. Jensen, A.S. Henriksen, N. Frimodt-Møller

Pivmecillinam: Estimation of adequate dosage for susceptible and ESBL-producing E. coli by Monte Carlo PK/PD simulation

Summary:

In the Scandinavian countries, pivmecillinam is widely used for treatment of urinary tract infections (UTI). In the present study we estimated the probability of target attainment in serum for a number of pivmecillinam dosage regimens for two different E. coli MIC levels: 0.125 - 0.5 mg/L and 1 - 2 mg/L (ESBL).

Pharmacokinetic data for mecillinam concentrations after per oral dosing of 400 mg pivmecillinam: 11 measurements of serum concentration within 8 hours from intake were recorded in 17 healthy volunteers.

The NPAG estimation program was used to fit a 6-parameter compartment model to the data, and Monte Carlo simulations were then made with the PKPDsim software.

With a target T>MIC of 40%, a PTA of 95% could be reached for MIC = 0.25 mg/L (simulated population dosed 400 mg pivmecillinam q8h). For MIC = 1 mg/L, a similar PTA required 800 mg q6h.

Additional search terms: breakpoints, population PK model parameters, probability of target attainment