Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites
Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5′-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosph...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-03-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383515001434 |
| _version_ | 1819034894155644928 |
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| author | Lingli Mu Rui Zhou Fang Tang Xingling Liu Sanwang Li Feifan Xie Xiang Xie Jie Peng Peng Yu |
| author_facet | Lingli Mu Rui Zhou Fang Tang Xingling Liu Sanwang Li Feifan Xie Xiang Xie Jie Peng Peng Yu |
| author_sort | Lingli Mu |
| collection | DOAJ |
| description | Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5′-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable. |
| first_indexed | 2024-12-21T07:40:59Z |
| format | Article |
| id | doaj.art-ccdecbcda96e45118b899d9f8abbc358 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-21T07:40:59Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-ccdecbcda96e45118b899d9f8abbc3582022-12-21T19:11:19ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432016-03-016215816210.1016/j.apsb.2015.10.002Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolitesLingli Mu0Rui Zhou1Fang Tang2Xingling Liu3Sanwang Li4Feifan Xie5Xiang Xie6Jie Peng7Peng Yu8Medical College, Hunan Normal University, Changsha 410006, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaMedical College, Hunan Normal University, Changsha 410006, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaZidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5′-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.http://www.sciencedirect.com/science/article/pii/S2211383515001434LC–MS/MSZidovudineMetabolitesPhosphateshPBMCshPBMCsPharmacokineticsIntracellular kinetic |
| spellingShingle | Lingli Mu Rui Zhou Fang Tang Xingling Liu Sanwang Li Feifan Xie Xiang Xie Jie Peng Peng Yu Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites Acta Pharmaceutica Sinica B LC–MS/MS Zidovudine Metabolites Phosphates hPBMCs hPBMCs Pharmacokinetics Intracellular kinetic |
| title | Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites |
| title_full | Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites |
| title_fullStr | Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites |
| title_full_unstemmed | Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites |
| title_short | Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites |
| title_sort | intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites |
| topic | LC–MS/MS Zidovudine Metabolites Phosphates hPBMCs hPBMCs Pharmacokinetics Intracellular kinetic |
| url | http://www.sciencedirect.com/science/article/pii/S2211383515001434 |
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