A Phase 1 Randomized, Placebo-Controlled Study Assessing the Pharmacokinetics, Safety, and Tolerability of Retosiban in Healthy, Nonpregnant Japanese Subjects.

This study characterized the pharmacokinetics, safety, and tolerability of retosiban in healthy, nonpregnant Japanese women prior to the enrollment of Japanese women in preterm labor in phase 3 trials. This study had 2 cohorts. Cohort 1 was a double-blind, sponsor-open, randomized study in Japanese women.

The pharmacokinetics and safety of darapladib in subjects with severe renal impairment.

Aim: Darapladib is a potent and reversible orally active inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2 ). The aim of the study was to assess the effects of severe renal impairment on the pharmacokinetics and safety/tolerability of darapladib compared with normal renal function.

Methods: This was an open label, parallel group study of darapladib following 10 day once daily 160 mg oral dosing in subjects with normal (n = 8) and severe renal impairment (estimated glomerular filtration rate <30 ml min(-1) 1.

An effect of moderate hepatic impairment on the pharmacokinetics and safety of darapladib.

Aim/methods: This was a phase 1, open label, non-randomized study designed to assess the pharmacokinetics and safety/tolerability of 10 consecutive once daily 40 mg oral doses of darapladib in subjects with moderate hepatic impairment (n = 12) compared with matched healthy volunteers (n = 12).

Results: For total darapladib, a small increase in total and peak exposure was observed in the subjects with moderate hepatic impairment compared with the subjects with normal hepatic function. The area under the plasma concentration-time curve during a dosing interval of duration τ (AUC(0,τ), geometric mean 223 ng ml(-1)  h [90% CI 158, 316 ng ml(-1 ) h], in moderate hepatic impaired subjects, vs.

Pharmacokinetic and pharmacodynamic interactions between diltiazem and methylprednisolone in healthy volunteers.

Objectives: The pharmacokinetics and pharmacodynamics after administration of methylprednisolone alone, diltiazem alone, and both drugs jointly were assessed in healthy volunteers.

Methods: An unblinded, controlled, fixed-sequence, 2-period study was carried out in 5 healthy white men who received a single dose of intravenous methylprednisolone, 0.3 mg/kg, on day 2, followed by diltiazem alone, 180 mg, on days 5, 6, and 7, with joint dosing of both drugs on day 8.

Pharmacokinetic/pharmacodynamic model for prednisolone inhibition of whole blood lymphocyte proliferation.

Aims: Mitogen-induced ex vivo whole blood lymphocyte proliferation (WBLP) is a widely used method to assess lymphocyte responsiveness to immunosuppressive therapy. A three-component complex model was developed to characterize effects of prednisolone on cell trafficking, transduction, and lymphocyte suppression.

Methods: An oral dose (0.