Efficacy and safety of the histamine H receptor antagonist ZPL-3893787 in patients with atopic dermatitis.

Background: H receptor antagonists are potential novel treatments for inflammatory skin diseases, including atopic dermatitis (AD).

Objective: We sought to study the efficacy and safety of ZPL-3893787 (a selective H receptor antagonist) in patients with moderate-to-severe AD.

Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30 mg) once-daily oral therapy in adults with moderate-to-severe AD.

Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms.

PF-184298 ((S)-2,3-dichloro-N-isobutyl-N-pyrrolidin-3-ylbenzamide) and PF-4776548 ((3-(4-fluoro-2-methoxy-benzyl)-7-hydroxy-8,9-dihydro-3H,7H-pyrrolo[2,3-c][1,7]naphthyridin-6-one)) are novel compounds which were selected to progress to human studies. Discordant human pharmacokinetic predictions arose from pre-clinical in vivo studies in rat and dog, and from human in vitro studies, resulting in a clearance prediction range of 3 to >20 mL min⁻¹ kg⁻¹ for PF-184298, and 5 to >20 mL min⁻¹ kg⁻¹ for PF-4776548. A package of work to investigate the discordance for PF-184298 is described.

No clinically significant pharmacokinetic interactions between voriconazole and indinavir in healthy volunteers.

Aims: Voriconazole is a new triazole antifungal agent, and is metabolized by the cytochrome P450 isoenzymes CYP2C9, CYP2C19 and to a lesser extent by CYP3A4. Protease inhibitors, such as indinavir, are also metabolized by cytochrome P450 (mainly CYP3A4). As these drugs are likely to be coadministered, these studies were performed to assess the pharmacokinetic interactions, safety and toleration of these drugs when taken together.

Effect of omeprazole on the steady-state pharmacokinetics of voriconazole.

Aims: Voriconazole, a novel triazole antifungal agent, is metabolized by the cytochrome P450 isoenzymes CYP2C19, CYP2C9, and to a lesser extent by CYP3A4. Omeprazole, a proton pump inhibitor used widely for the treatment of gastric and duodenal ulcers, is predominantly metabolized by CYP2C19 and CYP3A4. The aim of this study was to determine the effects of omeprazole on the steady-state pharmacokinetics of voriconazole.

Histamine H2-receptor antagonists have no clinically significant effect on the steady-state pharmacokinetics of voriconazole.

Aims: Voriconazole, a new triazole antifungal agent, is metabolized mainly by cytochrome P450s CYP2C19 and CYP2C9, and also by CYP3A4. The aim of this open-label, placebo-controlled, randomized, three-way crossover study was to determine the effects of cimetidine and ranitidine on the steady-state pharmacokinetics of voriconazole.

Methods: Twelve healthy male subjects received oral voriconazole 200 mg twice daily plus cimetidine 400 mg twice daily, voriconazole 200 mg twice daily plus ranitidine 150 mg twice daily, and voriconazole 200 mg twice daily plus placebo twice daily.

Voriconazole does not affect the steady-state pharmacokinetics of digoxin.

Aims: Voriconazole is a triazole antifungal agent with potent fungicidal activity against Aspergillus species. Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. This aim of this study was to investigate the effect of multiple-dose voriconazole on the steady-state pharmacokinetics of digoxin in healthy male volunteers.

Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration.

Aims: Voriconazole is a new triazole antifungal agent, and is metabolized by the cytochrome P450 isoenzymes CYP2C9, CYP2C19, and, to a lesser extent, by CYP3A4. Phenytoin is an inducer of CYP3A4 activity, and a substrate and inducer of CYP2C9 and CYP2C19. The present studies investigated the pharmacokinetic interactions of voriconazole and phenytoin when coadministered.

No clinically significant effect of erythromycin or azithromycin on the pharmacokinetics of voriconazole in healthy male volunteers.

Aims: The antibiotic erythromycin is a potent inhibitor of cytochrome P450 CYP3A4 metabolism. As CYP isozymes, including CYP3A4, are involved in the metabolism of the new triazole voriconazole, this study investigated the effects of multiple-dose erythromycin or azithromycin on the steady-state pharmacokinetics of voriconazole in healthy male subjects.

Methods: In an open, randomized, parallel-group, single-centre study, 30 healthy male subjects aged 20-41 years received oral voriconazole 200 mg twice daily for 14 days plus either erythromycin (1 g twice daily on days 8-14), azithromycin (500 mg once daily on days 12-14) or placebo (twice daily on days 8-14).

Voriconazole potentiates warfarin-induced prothrombin time prolongation.

Aims: Voriconazole is a novel triazole with broad-spectrum antifungal activity. It is likely that some patients receiving voriconazole may also require treatment with the anticoagulant warfarin. Cytochrome P450 isoenzymes are important in the metabolism of both these drugs.

Effect of food on the pharmacokinetics of multiple-dose oral voriconazole.

Aims: Voriconazole is a new triazole antifungal agent with activity against a range of clinically important and emerging pathogens. This study determined the effect of food on the pharmacokinetics of voriconazole in healthy volunteers.

Methods: This was an open, randomized, two-way crossover, multiple-dose study in male volunteers.

Voriconazole, a novel wide-spectrum triazole: oral pharmacokinetics and safety.

Aims: Voriconazole is a potent new triazole with broad-spectrum antifungal activity against clinically significant and emerging pathogens. The present study evaluated the safety, toleration, and pharmacokinetics of oral voriconazole after single and multiple dosing.

Methods: Sixty-four healthy subjects were randomized to receive treatment and 56 completed the study.

The pharmacokinetics and safety of intravenous voriconazole - a novel wide-spectrum antifungal agent.

Aims: Voriconazole is a new triazole with broad-spectrum antifungal activity against clinically significant and emerging pathogens. These studies evaluated the pharmacokinetics and safety of intravenous voriconazole in healthy male volunteers.

Methods: Two single-blind, placebo-controlled studies were conducted.