Darunavir concentration in PBMCs may be a better indicator of drug exposure in HIV patients
| Autor: | Fumito Gohda, Tomonori Nakamura, Yoshiyuki Ogawa, Koujirou Yamamoto, Hideki Uchiumi, Daisuke Nagano, Takuya Araki, Hiroshi Handa, Kunio Yanagisawa |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Male media_common.quotation_subject 030106 microbiology HIV Infections Pharmacology 030226 pharmacology & pharmacy Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Cell Line Tumor medicine Humans Pharmacology (medical) Drug Interactions Darunavir media_common Ritonavir business.industry General Medicine HIV Protease Inhibitors Middle Aged In vitro Leukocytes Mononuclear Trough level Female Efflux business medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 74(8) |
| ISSN: | 1432-1041 |
| Popis: | The clinical efficacies of some antiretroviral drugs are known to not depend on its concentration in blood. To establish a method of dosage adjustment for darunavir (DRV) based on pharmacokinetic theory, we analyzed the correlation between DRV levels in peripheral blood mononuclear cells (PBMCs) and plasma. The concentrations of DRV and ritonavir (RTV) in plasma and PBMCs of 31 samples obtained from 19 patients were analyzed. An in vitro kinetic study using MOLT-4 cells was performed to assess the contribution of RTV to the intracellular accumulation of DRV. DRV levels in PBMCs varied between 7.91 and 29.36 ng/106 cells (CV 37.5%), while those in plasma were greater. No significant correlation was found between the trough level of DRV in plasma and that in PBMCs (p = 0.575). The inter-day difference in DRV levels in PBMCs seemed smaller than that in plasma (− 41.6–23.0% vs − 83.3–109.1%). In the in vitro study, the elimination half-life of cellular efflux of DRV was 15.7 h in the absence of RTV and extended to 47.6 h in the presence of RTV. We found a poor correlation between intracellular DRV and plasma DRV levels in patients receiving highly active antiretroviral therapy. The efflux rate of DRV from cells was slow; therefore, the concentration of DRV in PBMCs may reflect average exposure to the drug and clinical efficacy. |
| Databáze: | OpenAIRE |
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