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Drug-drug interactions between lopinavir and felodipine in vitro and in vivo
Wanshu Li1, Yuxin Shen2, Qingqing Li1
1Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, Zhejiang, China.
Abstract:
This study investigated the drug-drug interaction (DDI) between the human immunodeficiency virus (HIV) medication lopinavir and the antihypertensive drug felodipine using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). In vitro assays showed the Michaelis constant (Km) values of lopinavir were measured at 32.59 μM and 14.04 μM in rat liver microsomes (RLM) and human liver microsomes (HLM), respectively. The half maximal inhibitory concentration (IC50) of felodipine for lopinavir was 21.84 μM and 19.47 μM in RLM and HLM, respectively. The results indicated that felodipine significantly inhibited the metabolism of lopinavir. In the metabolic stability experiment of RLM and HLM, the clearance rate was decreased by 97.28% and 53.32%, while the elimination half time (t1/2) was increased by 35.80 and 1.14 times, respectively. Further experiments indicated that felodipine inhibited lopinavir via competitive inhibition and mixed inhibition in RLM and HLM. Pharmacokinetic studies in rats demonstrated that the AUC(0-t) and AUC(0-∞) of lopinavir in the presence of felodipine was increased by 1.56-fold and 1.55-fold, respectively, compared with those in the control group. In addition, plasma clearance (CLz/F) in the co-administration group was decreased to 65.71% compared to the control group. However, felodipine did not significantly alter the pharmacokinetic parameters of ritonavir. This study explored the interaction between lopinavir and felodipine in vitro and in vivo, enhancing the data backing for clinical research.
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