Experiments for a systematic comparison between stable-isotope-(deuterium) labeling and radio-((14)C) labeling for the elucidation of the in vitro metabolic pattern of pharmaceutical drugs.

A systematic comparison between two labeling approaches for the investigation of the in vitro metabolic pattern of pharmaceutical drugs was performed by examining the use of (i) radiolabeled drugs analyzed with LC-MS-offline radiodetection and (ii) stable-isotope labeled drugs, used in a defined mixture with the unlabeled drug and analyzed by LC-MS with recognition of the specific isotopic pattern. (14)C was used for the radioisotope-approach and deuterium for the stable-isotope approach. Olanzapine, diclofenac and ketoconazole were chosen as model drugs, as they are commercially available in their non-, radio- and stable-isotope labeled forms.

Influence of food on the pharmacokinetics of oral alitretinoin (9-cis retinoic acid).

Background: Previous studies have shown that concomitant administration of food may enhance the bioavailability of oral retinoids.

Aim: To assess the influence of food on the pharmacokinetics (PK) of alitretinoin after a single oral dose.

Methods: This was a single-dose, open-label, randomized, crossover study, which enrolled 30 healthy men, aged 18-44 years.

Low levels of alitretinoin in seminal fluids after repeated oral doses in healthy men.

Background: Alitretinoin, like all retinoids, is teratogenic, and can only be given to women of childbearing potential if pregnancy is excluded and a strict contraceptive programme is followed.

Aim: This study was designed to determine whether alitretinoin in the semen of men treated with alitretinoin poses a teratogenic risk to their female partners.

Methods: In total, 24 healthy men aged 18-45 years received alitretinoin 20 mg (n = 12) or 40 mg (n = 12), once daily for 14 days.

Influence of alitretinoin on the pharmacokinetics of the oral contraceptive ethinyl estradiol/norgestimate.

Background: Alitretinoin (9-cis retinoic acid) is currently registered in many European countries and in Canada as the only licensed treatment for severe chronic hand eczema unresponsive to potent topical corticosteroids. Alitretinoin, like all retinoids, is teratogenic, and women of child-bearing potential must strictly adhere to pregnancy-prevention measures.

Aim: To investigate the influence of alitretinoin on the pharmacokinetics (PK) of ethinyl estradiol/norgestimate (Ortho Tri-Cyclen 28(®)), a commonly prescribed combination oral contraceptive.

Investigation of the species-dependent in vitro metabolism of BAL30630 by stable isotope labeling and isotope exchange experiments analyzed by capillary liquid chromatography coupled to mass spectrometry.

The in vitro metabolic profile of BAL30630, an antifungal piperazine propanol derivative, which inhibits the 1,3-beta-D-glucansynthase, was investigated by incubation with microsomes of several species and with rat hepatocytes. For the spotting of the metabolites, mixtures of BAL30630 with a stable isotope (deuterium) labeled analogue were incubated. The metabolic pattern comprises several oxidized metabolites.