Innovative Study Design

Here at ICPD, we pride ourselves on our innovative study designs. From glassware to mice to man, our novel study designs have provided the opportunity to gain new insights into the pharmacokinetics-pharmacodynamics (PK-PD) of drugs. PK-PD-based studies allow better discrimination of drug effect and hold the promise to change how drugs are developed today and in the future.

One Recent Application

The relationship between drug exposure and the time course of antimicrobial effect at the primary infection site for acute maxillary sinusitis had not previously been explored. We used a new technique to determine the time course of gatifloxacin effect in the treatment of acute maxillary sinusitis. Our approach involved the insertion of an indwelling catheter into the maxillary sinus, which allowed for serial sinus aspirate sampling. This approach allowed for us to describe the time-course of drug concentrations at the effect site, the time-course of sinus sterilization, which allowed better characterization of drug effect. Below are two figures. The upper panel (Figure 1) shows the time course of drug concentrations in plasma and sinus. The lower panel (Figure 2) shows an inverted Kaplin-Meier plot depicting the time course of sinus sterilization for pneumococci. This study was the first ever to demonstate drug exposure and the rate of bacterial clearance in the maxillary sinus.

Figure 1. Median predicted steady state gatifloxacin concentration versus time profile in plasma samples and sinus aspirates, with a representative patient insert. Solid line, predicted plasma concentrations; dashed line, predicted sinus concentrations; filled circle symbols, observed plasma concentrations; empty square symbols, observed sinus concentrations.

Figure 2. Inverted Kaplan-Meier plot of the time course of sinus sterilization for pneumococci. The times to median and 75% sinus sterilization were 50 hours and 64.5 hours, respectively.