Metabolism and pharmacokinetics of indacaterol in humans
| Autor: | Jeremy G. Dain, Christine Reynolds, Lana Peng, Mark Kagan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Metabolic Clearance Rate Metabolite Pharmaceutical Science Administration Oral Urine Pharmacology Quinolones Hydroxylation Models Biological Excretion chemistry.chemical_compound Feces Glucuronides Pharmacokinetics Tandem Mass Spectrometry medicine Humans Carbon Radioisotopes Adrenergic beta-2 Receptor Agonists Biotransformation Chromatography Inhalation Molecular Structure Half-life chemistry Area Under Curve Indans Indacaterol Glucuronide medicine.drug Chromatography Liquid Half-Life |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 40(9) |
| ISSN: | 1521-009X |
| Popis: | The metabolism, pharmacokinetics, and excretion of [(14)C]indacaterol were investigated in healthy male subjects. Although indacaterol is administered to patients via inhalation, the dose in this study was administered orally. This was done to avoid the complications and concerns associated with the administration of a radiolabeled compound via the inhalation route. The submilligram doses administered in this study made metabolite identification and structural elucidation by mass spectrometry especially challenging. In serum, the mean t(max), C(max), and AUC(0-last) values were 1.75 h, 0.47 ng/ml, and 1.81 ng · h/ml for indacaterol and 2.5 h, 1.4 ngEq/ml, and 27.2 ngEq · h/ml for total radioactivity. Unmodified indacaterol was the most abundant drug-related compound in the serum, contributing 30% to the total radioactivity in the AUC(0-24h) pools, whereas monohydroxylated indacaterol (P26.9), the glucuronide conjugate of P26.9 (P19), and the 8-O-glucuronide conjugate of indacaterol (P37) were the most abundant metabolites, with each contributing 4 to 13%. In addition, the N-glucuronide (2-amino) conjugate (P37.7) and two metabolites (P38.2 and P39) that resulted from the cleavage about the aminoethanol group linking the hydroxyquinolinone and diethylindane moieties had a combined contribution of 12.5%. For all four subjects in the study, ≥90% of the radioactivity dose was recovered in the excreta (85% in feces and 10% in urine, mean values). In feces, unmodified indacaterol and metabolite P26.9 were the most abundant drug-related compounds (54 and 17% of the dose, respectively). In urine, unmodified indacaterol accounted for ∼0.3% of the dose, with no single metabolite accounting for >1.3%. |
| Databáze: | OpenAIRE |
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