Severe cholestatic hepatitis caused by azathioprine.

A male patient receiving azathioprine treatment for discoid lupus erythematodes developed severe cholestatic hepatitis between 14 and 21 days after initiation of the treatment with peak bilirubin levels of 62.4 mg/dL. Other causes of hepatic dysfunction including viral hepatitis were clinically and serologically excluded.

Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

Background: Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach.

Objectives: Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data.

Design: Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.