Population Pharmacokinetics of Paritaprevir, Ombitasvir, and Ritonavir in Japanese Patients with Hepatitis C Virus Genotype 1b Infection

Abstract

Population pharmacokinetic modeling did not reveal any patient-related or clinical parameters that would require dose adjustment of the 2D regimen when used for the treatment of HCV genotype 1b infection in Japanese patients.

Pharmacokinetics, Safety, and Tolerability of Glecaprevir and Pibrentasvir in Healthy White, Chinese, and Japanese Adult Subjects

“…Pibrentasvir exposures following 7 days of QD dosing (80, 120, or 160 mg) across white, Han Chinese, and Japanese subjects are summarized in Table 2. The percentage differences in C max and AUC 24 between Japanese and whites ranged from 4% to 52% and 1% to 51%, respectively, and the percentage differences in C max and AUC 24 between Han Chinese and whites were from 6% to 36% and 14% to 24%, respectively, across 3 pibrentasvir doses evaluated in the 2 studies. Pibrentasvir showed a slightly less-thandose-proportional increase in exposures from 80 mg to 160 mg in white, Han Chinese, and Japanese subjects.…”

“…The maximum plasma concentration (C max ), time to C max , and plasma concentration at 24 hours after dosing were determined directly from the plasma concentrationtime data. Estimated pharmacokinetic parameters included the terminal phase elimination half-life, and the area under the concentration-time curve from time 0 to 24 hours (AUC 24 ).…”

“…To assess the effect of pibrentasvir on glecaprevir or vice versa in different dose combinations, a repeatedmeasures analysis was performed for the natural logarithms of glecaprevir or pibrentasvir C max and AUC 24 utilizing data from days 7 (glecaprevir or pibrentasvir alone) and 14 (glecaprevir and pibrentasvir coadministration) in each dose combination. The initial model had day, race/ethnicity, and 2-factor interaction of day and race/ethnicity as fixed effects and day as the repeated factor.…”

“…No statistically significant differences in glecaprevir and pibrentasvir C max and AUC 24 values were observed between Japanese or Han Chinese and white subjects following the phase 3 doses of glecaprevir/pibrentasvir 300 mg/120 mg QD administration; 1 exception was a slightly lower AUC 24 value observed in Han Chinese when comparing to that in whites ( Figure 3). AUC 24 indicates area under the plasma concentration-time curve from time 0 to 24 hours; C 24 , plasma concentration at 24 hours postdose; C max , maximum observed plasma concentration; CV%, coefficient of variation percentage. Highlighted row indicates the clinical doses of glecaprevir 300 mg and pibrentasvir 120 mg. a For pibrentasvir 80 mg, N = 8 for Han Chinese; for pibrentasvir 160 mg, N = 5 for Han Chinese.…”

Development of glucose-responsive ‘smart’ insulin systems

“…Development of novel insulin analogs with more rapid onset of activity and shorter duration of action (relative to current insulin analog products Humalog ® , Novolog ® , and Apidra ® (40-42)) could improve closed-loop systems by providing more predicable pharmacodynamic profiles and hence more accurate calculation of insulin doses. Examples of more rapid formulations are provided by Novolog-based FIAsp (a reformulation of insulin aspart to contain excepients that promote capillary absorption) or addition of the degradative enzyme hyaluronidase to wild-type insulin (rHuPH20; Halozyme, Inc.) (43, 44*, 45*); the latter approach is no longer being pursued.…”