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. 2016 Mar;6(Suppl 1):S15–S26. doi: 10.1086/685017

Table 4.

Point estimates (least squares means) and 2-sided 90% CIs of selected pharmacokinetic parameters for total and unbound riociguat and metabolite M1 in plasma from patients with mild, moderate, or severe renal impairment versus those in plasma from individuals with normal renal function, following a single oral dose of riociguat 1.0 mg in the mixed population of smokers and nonsmokers

Comparison, parameter n CV, % Estimated ratio, % 90% CI
Riociguat (total)
 Mild vs. normal
  AUCnorm 31 98 143 87.1–234
  Cmax, norm 31 29 113 95.4–134
 Moderate vs. normal
  AUCnorm 32 98 204 126–332
  Cmax, norm 32 29 115 97.5–136
 Severea vs. normal
  AUCnorm 32 98 144 88.6–234
  Cmax, norm 32 29 96.6 81.7–114
Metabolite M1 (total)
 Mild vs. normal
  AUCnorm 31 39 101 81.0–127
  Cmax, norm 31 58 76.1 55.2–105
 Moderate vs. normal
  AUCnorm 32 39 163 131–204
  Cmax, norm 32 58 81.1 59.1–111
 Severea vs. normal
  AUCnorm 32 39 175 140–218
  Cmax, norm 32 58 86.4 63.0–119
Riociguat (unbound)
 Mild vs. normal
  AUCu, norm 31 103 130 78.0–217
  Cmax, u, norm 31 34 103 84.8–126
 Moderate vs. normal
  AUCu, norm 32 103 218 132–360
  Cmax, u, norm 32 34 123 101–149
 Severea vs. normal
  AUCu, norm 32 103 174 105–288
  Cmax, u, norm 32 34 117 96.2–142
Metabolite M1 (unbound)
 Mild vs. normal
  AUCu, norm 31 40 94.6 75.1–119
  Cmax, u, norm 31 59 70.7 50.9–98.2
 Moderate vs. normal
  AUCu, norm 32 40 181 144–227
  Cmax, u, norm 32 59 89.7 64.9–124
 Severea vs. normal
  AUCu, norm 32 40 233 186–293
  Cmax, u, norm 32 59 115 83.4–159
Note

AUCnorm: area under the plasma concentration–time curve from time 0 to infinity divided by dose of riociguat per kilogram body weight for total riociguat/M1; AUCu, norm: area under the plasma concentration–time curve from time 0 to infinity divided by dose of riociguat per kilogram body weight for unbound riociguat/M1; Cmax, norm: maximum concentration in plasma divided by dose of riociguat per kilogram body weight for total riociguat/M1; Cmax, u, norm: maximum concentration in plasma divided by dose of riociguat per kilogram body weight for unbound riociguat/M1; CI: confidence interval; CV: coefficient of variation.

a

In study I, individuals with severe renal impairment received riociguat 0.5 mg, and therefore pharmacokinetic concentrations recorded for these individuals were normalized to a 1.0-mg dose before analysis; all other participants in both studies received riociguat 1.0 mg.