Dataset from An Open Label Study in Healthy Volunteers to Investigate the Effect of Ketoconazole on the Pharmacokinetics of GSK239512

The study will determine the effect of 400 mg once daily of ketoconazole at steady state on the pharmacokinetics of a single oral dose of GSK239512 in young healthy volunteers. Ketoconazole is a strong inhibitor of CYP3A4, which is involved in metabolism of drugs. A two-cohort design will be applied with cohort 1 aimed at providing a first estimate of the interaction potential of GSK239512 and ketoconazole in terms of pharmacokinetic parameters in a small number of subjects. Data from Cohort 1 will inform the decision of which dose to use in Cohort 2, in which a larger number of subjects will be exposed to GSK239512 without and with ketoconazole. The target maximum exposure is aimed to be similar to the exposure by a single dose of 80 mcg of GSK239512 without CYP3A4 inhibition. In summary, the results from this study will help to estimate the maximum increase in exposure of GSK239512 during concomitant use of strong CYP3A4 inhibitors and will help define the subsequent dosing strategy around GSK239512 and co-medications with potential to inhibit CYP3A4.

本研究旨在考察稳态下每日一次400mg酮康唑对年轻健康受试者单次口服给予GSK239512的药代动力学的影响。酮康唑为强效细胞色素P450 3A4（CYP3A4）抑制剂，该酶参与药物代谢。本研究采用两队列设计，队列1旨在在少量受试者中初步评估GSK239512与酮康唑的药代动力学相互作用潜力；队列1的数据将为队列2的给药剂量选择提供依据，队列2中将有更多受试者分别在未合用与合用酮康唑的情况下暴露于GSK239512。本研究的目标最大暴露量拟与未合用CYP3A4抑制剂时单次给予80μg GSK239512的暴露量相当。综上，本研究结果将有助于估算合用强效CYP3A4抑制剂期间GSK239512暴露量的最大增幅，并可明确GSK239512与潜在CYP3A4抑制性合并用药的后续给药策略。