Influence of SLCO1B1 polymorphisms on lopinavir Ctrough in Serbian HIV/AIDS patients
© 2020 The British Pharmacological Society..
AIMS: Lopinavir (LPV) is not a first-line regimen. According to recent WHO data, LPV usage in low- and middle-income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (Ctrough ) in Serbian patients.
METHODS: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV Ctrough was quantified using liquid-chromatography-mass spectrometry. Genotyping was carried out using real-time-PCR-based allelic discrimination. One-way analysis of variance, t test and linear regression were used for data analysis.
RESULTS: The overall mean (SD) LPV Ctrough was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median Ctrough = 6072 ng/mL, interquartile range (IQR) = 4318-7617 ng/mL), CA (LPV median Ctrough = 4987 ng/mL, IQR = 4300-6295 ng/mL) and AA (LPV median Ctrough = 3648 ng/mL, IQR = 1949-4072 ng/mL) (P = .005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median Ctrough = 6027 ng/mL, IQR =4548-8250 ng/mL), CT (LPV median Ctrough = 5553 ng/mL, IQR = 4300-6888 ng/mL) and TT (LPV median Ctrough = 4408 ng/mL, IQR = 3361-5233 ng/mL) (P = .007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median Ctrough = 5434 ng/mL, IQR = 3855-6830 ng/mL), heterozygotes (LPV median Ctrough = 6707 ng/mL, IQR = 5088-8063 ng/mL) and C-homozygotes (LPV median Ctrough = 13906 ng/mL, IQR = 12946-14866 ng/mL) was observed (P = .002). In multivariate regression analysis, only the SLCO1B1 rs4149056 polymorphism was independently associated with higher LPV Ctrough (β = 2834.5 [1442-4226.9] ng/mL [P = .001]).
CONCLUSIONS: Our results demonstrate a statistically significant influence of the SLCO1B1 rs4149056 polymorphism on higher LPV Ctrough in Caucasian HIV/AIDS patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:86 |
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| Enthalten in: |
British journal of clinical pharmacology - 86(2020), 7 vom: 30. Juli, Seite 1289-1295 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dragović, Gordana [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.07.2021 Date Revised 26.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bcp.14230 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306170736 |
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| 100 | 1 | |a Dragović, Gordana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Influence of SLCO1B1 polymorphisms on lopinavir Ctrough in Serbian HIV/AIDS patients |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 26.07.2021 | ||
| 500 | |a Date Revised 26.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The British Pharmacological Society. | ||
| 520 | |a AIMS: Lopinavir (LPV) is not a first-line regimen. According to recent WHO data, LPV usage in low- and middle-income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (Ctrough ) in Serbian patients | ||
| 520 | |a METHODS: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV Ctrough was quantified using liquid-chromatography-mass spectrometry. Genotyping was carried out using real-time-PCR-based allelic discrimination. One-way analysis of variance, t test and linear regression were used for data analysis | ||
| 520 | |a RESULTS: The overall mean (SD) LPV Ctrough was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median Ctrough = 6072 ng/mL, interquartile range (IQR) = 4318-7617 ng/mL), CA (LPV median Ctrough = 4987 ng/mL, IQR = 4300-6295 ng/mL) and AA (LPV median Ctrough = 3648 ng/mL, IQR = 1949-4072 ng/mL) (P = .005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median Ctrough = 6027 ng/mL, IQR =4548-8250 ng/mL), CT (LPV median Ctrough = 5553 ng/mL, IQR = 4300-6888 ng/mL) and TT (LPV median Ctrough = 4408 ng/mL, IQR = 3361-5233 ng/mL) (P = .007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median Ctrough = 5434 ng/mL, IQR = 3855-6830 ng/mL), heterozygotes (LPV median Ctrough = 6707 ng/mL, IQR = 5088-8063 ng/mL) and C-homozygotes (LPV median Ctrough = 13906 ng/mL, IQR = 12946-14866 ng/mL) was observed (P = .002). In multivariate regression analysis, only the SLCO1B1 rs4149056 polymorphism was independently associated with higher LPV Ctrough (β = 2834.5 [1442-4226.9] ng/mL [P = .001]) | ||
| 520 | |a CONCLUSIONS: Our results demonstrate a statistically significant influence of the SLCO1B1 rs4149056 polymorphism on higher LPV Ctrough in Caucasian HIV/AIDS patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HIV/AIDS | |
| 650 | 4 | |a SLCO1B1 | |
| 650 | 4 | |a lopinavir | |
| 650 | 4 | |a pharmacokinetic | |
| 650 | 4 | |a single nucleotide polymorphism | |
| 650 | 7 | |a HIV Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Liver-Specific Organic Anion Transporter 1 |2 NLM | |
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| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Dimitrijević, Božana |e verfasserin |4 aut | |
| 700 | 1 | |a Kušić, Jovana |e verfasserin |4 aut | |
| 700 | 1 | |a Soldatović, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Jevtović, Djordje |e verfasserin |4 aut | |
| 700 | 1 | |a Olagunju, Adeniyi |e verfasserin |4 aut | |
| 700 | 1 | |a Owen, Andrew |e verfasserin |4 aut | |
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