Pharmacokinetics of vandetanib in subjects with renal or hepatic impairment.

Background And Objective: Vandetanib, an oncology drug being evaluated in phase III clinical trials, undergoes significant renal and hepatic excretion. The objective of these two studies was to investigate the single-dose pharmacokinetics of vandetanib in subjects with renal or hepatic impairment in comparison with healthy subjects.

Subjects And Methods: Two open-label, parallel-group studies were conducted at a single centre in Germany.

The pharmacokinetics of escitalopram in patients with hepatic impairment.

The effect of hepatic impairment on the pharmacokinetics of escitalopram was determined by means of nonlinear mixed effect modeling, considering both the Child-Pugh classification (and its components) and cytochrome P450 2C19 (CYP2C19) activity. Twenty-four subjects were grouped according to their Child-Pugh score as healthy, with mild hepatic impairment or with moderate hepatic impairment. The subjects were administered a single oral dose of escitalopram 20 mg, and blood was sampled up to 168 hours after dosage.

Pharmacokinetics and sedative effects in healthy subjects and subjects with impaired liver function after continuous infusion of clomethiazole.

Objective: Clomethiazole is virtually completely eliminated by hepatic metabolism. This study was designed to assess the impact of liver impairment on its elimination and sedative effects.

Methods: Eight patients with mild liver impairment (Child-Pugh grade A), eight patients with moderate/severe liver impairment (Child-Pugh grade B/C) and eight healthy subjects of similar age were given 68 mg/kg clomethiazole edisilate according to a 24-h infusion scheme aimed at producing minimum sedation as it was intended for clinical use in patients with stroke.