Figure 3. . Solithromycin N-acetylation rates in vitro in cryopreserved human hepatocytes from rapid, intermediate and slow acetylators.

Solithromycin N-acetylation rates in nmoles/min/mg protein are shown in (A–D). Solithromycin N-acetylation rates as percent conversion of solithromycin to N-acetyl-solithromycin are shown in (E–H). In each case, differences between rapid, intermediate and slow acetylators were analyzed by one-way analysis of variance, and p-values for significance of the differences are shown. Assays were conducted at multiple substrate concentrations: (A & E; 100 μM solithromycin and 100 μM AcCoA), (B & F; 1 mM solithromycin and 100 μM AcCoA), (C & G; 100 μM solithromycin and 1 mM AcCoA), and (D & H; 1 mM solithromycin and 1 mM AcCoA). Each bar represents mean ± standard error measured in six to seven samples of cryopreserved human hepatocytes. Rapid acetylator hepatocytes (black bars) consisted of NAT2*4/*4 (five samples) and NAT2*4/*13 (one sample). Intermediate acetylator hepatocytes (gray bars) consisted of NAT2*4/*5B (three samples), NAT2*4/*6A (one sample), NAT2*4/*5A (one sample), NAT2*4/*7B (one sample) and NAT2*4/*14B (one sample). Slow acetylator hepatocytes (white bars) consisted of NAT2*5B/*5B (two samples), NAT2*5B/*6A (three samples) and NAT2*6A/*6A (one sample). The sex and ethnicity of the samples were six female Caucasians, four male Caucasians, two male Hispanics, two female Hispanics and one male of African descent.

AcCoA: Acetyl coenzyme A.