Quantification of disease progression and dropout for Alzheimer's disease.

This research aimed to quantitatively describe the natural progression of Alzheimer's disease (AD) based on ADAScog scores in patients with mild-to-moderate AD. ADAS-cog data from 10 placebo-controlled clinical trials including more than 2,400 patients with up to 72 weeks of treatment were used. Different models describing the time course of ADAS-cog were evaluated.

Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113).

Background: Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting.

Methods: One-hundred and thirty HIV-1-infected adults with self-reported lipoatrophy confirmed by physical examination were randomized to receive pioglitazone 30 mg once daily (n=64) or placebo (n=66) for 48 weeks.

Use of an indirect effect model to describe the LDL cholesterol-lowering effect by statins in hypercholesterolaemic patients.

Statins are the most commonly prescribed agents for the treatment of hypercholesterolaemia. This is due to their efficacy in reducing low-density lipoprotein cholesterol (LDL) level which is the primary goal of the treatment especially for patients with multiple risk factors or with established coronary heart diseases. The purpose of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model that describes the LDL-lowering process in patients with hypercholesterolaemia treated with atorvastatin, fluvastatin or simvastatin.

Population pharmacokinetic study of methotrexate in patients with lymphoid malignancy.

Purpose: A population pharmacokinetic model was developed to describe dose-exposure relationships of methotrexate (MTX) in adults with lymphoid malignancy; this is in order to explore the interindividual variability in relationship with the different physiopathological variables. The final model was applied to the Bayesian estimation of MTX concentrations using two blood samples.

Methods: Fifty-one patients receiving 136 courses of MTX (1-6 per patient) were included in this study.

A mutation in the drug transporter gene ABCC2 associated with impaired methotrexate elimination.

Human multidrug resistance protein 2 (MRP2, encoded by ABCC2) is involved in active efflux of anionic drugs such as methotrexate. MRP2 is expressed on the luminal side of hepatocytes and renal proximal tubular cells, indicating an important role in drug elimination. We postulated that loss-of-function mutations in ABCC2, which are involved in the Dubin-Johnson syndrome, may be associated with impaired methotrexate elimination and an increased risk of toxicity.