A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication

Abstract

Background: Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited, therefore application of minimally invasive drug sampling techniques, such as dried blood spots (DBS), may enhance the enrollment of children in PK studies. The objectives of this study were to compare solithromycin concentrations in DBS with those in liquid plasma samples (LPS) and to quantify the effects of modeling DBS concentrations on the results of a population PK model.

Methods: Comparability analysis was performed on matched DBS and LPS solithromycin concentrations collected from two different phase 1 clinical trials of solithromycin treatment in children (clinicaltrials.gov #NCT01966055 and #NCT02268279). Comparability of solithromycin concentrations was evaluated based on DBS:LPS ratio, median percentage prediction error, and median absolute percentage prediction error. The effect of correcting DBS concentrations for both hematocrit and protein binding was investigated. In addition, a previously published population PK model (NONMEM) was leveraged to compare parameter estimates resulting from either DBS or LPS concentrations.

Results: A total of 672 paired DBS-LPS concentrations were available from 95 subjects (age: 0-17 years of age). The median (range) LPS and DBS solithromycin concentrations were 0.3 (0.01-12) mcg/mL and 0.32 (0.01-14) mcg/mL, respectively. Median percentage prediction error and median absolute percentage prediction error of raw DBS to LPS solithromycin concentrations were 5.26% and 22.95%, respectively. In addition, the majority of population PK parameter estimates resulting from modeling DBS concentrations were within 15% of those obtained from modeling LPS concentrations.

Conclusions: Solithromycin concentrations in DBS were similar to those measured in LPS and did not require correction for hematocrit or protein binding.

Figure 1.

Comparability analysis of matched dried blood spot (DBS) and liquid plasma samples (LPS) solithromycin concentrations. Panel a) shows the weighted linear regression of the paired LPS-DBS solithromycin concentrations. The solid and dashed lines represent the unity line and regression fit, respectively. Panel b) shows solithromycin DBS-LPS ratio versus LPS solithromycin concentration. The dashed lines denote the mean ratio and 1.96 × standard deviation. The solid black line denotes a ratio of 1. Three ratios > 7 were removed from the figure to allow for improved visualization of the data. Panel c) shows the paired LPS-DBS solithromycin concentrations plotted on a log scale.