Generics in transplantation medicine: Randomized comparison of innovator and substitution products containing mycophenolate mofetil .

Objective: Mycophenolate mofetil (MMF) is widely used as an immunosuppressant for the prophylaxis of acute organ rejection in recipients of solid organ transplants.

Materials And Methods: We have compared, in healthy subjects, the pharmacokinetics of mycophenolic acid when MMF was administered in the form of the innovator product CellCept (F. Hoffmann-La Roche Ltd.

A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).

Objectives: Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150).

Exposure-Exposure Relationship of Tocilizumab, an Anti-IL-6 Receptor Monoclonal Antibody, in a Large Population of Patients With Rheumatoid Arthritis.

Relationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies. Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints (DAS28) and American College of Rheumatology (ACR) criteria and with a decrease in inflammation markers. A population pharmacokinetic/pharmacodynamic (PKPD) model was developed to describe data from 2 studies.

Exposure-response relationship of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in a large population of patients with rheumatoid arthritis.

Relationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies. Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints (DAS28) and American College of Rheumatology (ACR) criteria and with a decrease in inflammation markers. A population pharmacokinetic/pharmacodynamic (PKPD) model was developed to describe data from 2 studies.

Tocilizumab has no clinically relevant effects on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

Objective: To assess the effects of tocilizumab on methotrexate and 7-hydroxymethotrexate pharmacokinetics in patients with rheumatoid arthritis and to explore the pharmacodynamic effect of tocilizumab on C-reactive protein (CRP), a marker of inflammation.

Methods: Methotrexate (10 - 25 mg) was administered orally on Days 1, 8, 15, 22, 29, 36, and 43. On Day 8 patients received 10 mg/kg tocilizumab intravenously.

Population pharmacokinetic analysis of tocilizumab in patients with rheumatoid arthritis.

Tocilizumab is a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody that has demonstrated efficacy in the treatment of rheumatoid arthritis (RA). A population pharmacokinetic (PK) model was developed using nonlinear mixed effect modeling to describe the PK profile of tocilizumab and used to estimate interindividual variability and assess the influence of covariates on PK parameters. The model was constructed based on data collected from 1793 patients with moderate to severe RA who received tocilizumab (4 or 8 mg/kg), via intravenous infusion every 4 weeks, during 4 phase III clinical trials.

Unexpected Hepatotoxicity of Rifampin and Saquinavir/Ritonavir in Healthy Male Volunteers.

OBJECTIVES: Rifampin is a potent inducer of the cytochrome P450 3A4 isoenzyme (CYP3A4) that metabolizes most protease inhibitor (PI) antiretrovirals. This study was designed to evaluate the steady-state pharmacokinetics and tolerability of the coadministration of the PIs saquinavir and ritonavir (a CYP3A4 inhibitor used as a pharmacoenhancer of other PIs) and rifampin when coadministered in healthy HIV-negative volunteers. METHODS: In an open-label, randomized, one sequence, two-period crossover study involving 28 healthy HIV-negative volunteers, arm 1 was randomized to receive saquinavir/ritonavir 1000/100 mg twice daily while arm 2 received rifampin 600 mg once daily for 14 days.

Saquinavir 500 mg film-coated tablets demonstrate bioequivalence to saquinavir 200 mg hard capsules when boosted with twice-daily ritonavir in healthy volunteers.

Objective: To establish the bioequivalence of a 500 mg film-coated tablet of saquinavir mesylate (FCT SQV) to the 200 mg hard-capsule saquinavir mesylate (HC SQV), both boosted with ritonavir and administered under fed conditions.

Methods: We carried out a multi-centre, open-label, randomized, two-sequence, four-period, two-treatment, replicated crossover study in 93 healthy men and 7 healthy women. Individuals were randomly assigned to receive sequential single doses of saquinavir in one of two treatment sequences: ABAB or BABA.

Significant effect of capecitabine on the pharmacokinetics and pharmacodynamics of warfarin in patients with cancer.

Purpose: Clinical cases of capecitabine and other fluorouracil-based chemotherapies potentiating the effects of coumarin derivatives have been reported. This study assessed the influence of capecitabine on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin.

Patients And Methods: Four patients with advanced/metastatic cancer completed the study, receiving a single oral dose of 20 mg warfarin before the start of standard capecitabine treatment (day 1), and again during the third cycle of capecitabine (day 61).

Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer.

Background: Capecitabine (Xeloda) is a novel, oral fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumor tissue via a three-step enzymatic cascade.

Purpose: The objective of this study was to compare the pharmacokinetics of capecitabine and its metabolites in Japanese and Caucasian cancer patients.

Methods: The study included 20 Japanese and 24 Caucasian patients with breast cancer.