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The pharmacokinetic (PK) characteristics of drugs were altered under high‐altitude hypoxia. We aim to describe the population PK of atorvastatin (ATV) to identify patient characteristics that are predictive of variability in the PK parameters of the ATV and investigate the effects of high‐altitude hypoxia on the blood concentration of ATV in patients with hyperlipidemia. A total of 160 plasma concentrations were collected from 40 patients with hyperlipidemia in plateau areas and 40 in plain areas. The population pharmacokinetic model of patients with hyperlipidemia in plateau and plain areas of China was established by a nonlinear mixed‐effects model. The PK of ATV were described by a 1‐compartment model with first‐order elimination. The main PK parameters of ATV were the first‐order absorption rate (0.76 hour−1 fixed); clearance (174.22 L/h) and apparent volume of distribution (1119.62 L). The values of area and age were identified as significant covariates for the clearance, area, age, and urea for the volume of distribution. The steady‐state peak concentration in the plateau area was higher than that in the plain area. This study may suggest dose reduction is necessary for patients with hyperlipidemia in high altitudes. [ABSTRACT FROM AUTHOR]

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. Cmax increased by 27% under the fed state. On repeat administration, negligible accumulation (<20%) of systemic exposures was observed for both formulations. Steady state was achieved within 48 hours of dosing with the XR formulation. Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. [ABSTRACT FROM AUTHOR]