Determination of nevirapine, an HIV-1 non-nucleoside reverse transcriptase inhibitor, in human plasma by reversed-phase high-performance liquid chromatography

Hollanders, R.M.F.; Kolmer, E.W.J. van Ewijk-Beneken; Burger, David M.; Wuis, E.W.; Koopmans, P.P.; Hekster, Y.A.

doi:10.1016/s0378-4347(00)00231-0

Cited by 55 publications

(40 citation statements)

References 6 publications

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“…176,2003) showed that the combination of NVP and EFZ did not provide additive benefit and, moreover, increased the adverse side effects. The present assay was also highly sensitive, with a detection limit of 100 pg ml Ϫ1 , which compares favorably with those previously reported for UV and tandem mass spectrometry methods: close to 50 (6,10,22) and 10 (14) ng ml Ϫ1 , respectively. The accuracy and precision of the EIA were also good, so the assay is useful for pharmacokinetic studies.…”

Section: Discussionsupporting

confidence: 89%

“…Several high-performance liquid chromatographic (HPLC) assays combined with UV detection (6,10,22) or tandem mass spectrometry (14,24) for the quantitative determination of NVP in plasma have been described. However, these methods are characterized by a relatively high limit of quantification (10 ng ml Ϫ1 ) and by fastidious workup, thus excluding their use in the ex vivo monitoring of intracellular levels of the drug.…”

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Sensitive Enzyme Immunoassay for Measuring Plasma and Intracellular Nevirapine Levels in Human Immunodeficiency Virus-Infected Patients

Azoulay

Nevers

Créminon

et al. 2004

Antimicrob Agents Chemother

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We have developed an enzyme immunoassay to measure nevirapine (NVP) in plasma and peripheral blood mononuclear cells. Anti-NVP polyclonal antibodies were raised in rabbits by using a synthetic NVP derivative coupled to keyhole limpet hemocyanin as the immunogen, and the enzyme tracer was prepared by chemically coupling the NVP derivative with acetylcholinesterase. These reagents were used to develop a sensitive competitive enzyme immunoassay performed in microtitration plates with a 100-pg ml ؊1 limit of detection and thus ϳ100 times more sensitive than previously published techniques. The plasma assay was performed directly without extraction (in this case, a 500-pg ml ؊1 limit of detection was observed) on a minimum of 30 l of plasma. This assay shows good precision and efficiency, since recovery from human plasma and cell extracts spiked with NVP ranged between 87 and 104%, with coefficients of variation of <10%. A pharmacokinetic analysis of plasma NVP was performed for seven patients infected with human immunodeficiency virus (HIV), and it gave results similar to published findings. Intracellular concentrations of NVP were measured in cultured human T-lymphoblastoid cells and peripheral blood mononuclear cells from HIV-infected patients. The results indicated a very low intracellular/extracellular concentration ratio (0.134), thus demonstrating the absence of intracellular drug accumulation. This is the first intracellular assay of a nonnucleoside reverse-transcriptase inhibitor, and this method could be useful in monitoring plasma and intracellular NVP levels in HIV-infected patients.Nevirapine (Viramune) (NVP) is a nonnucleoside reversetranscriptase inhibitor indicated for the treatment of human immunodeficiency virus (HIV) type 1 infection. It represents an attractive option for patients who prefer a protease-sparing regimen, because it can be taken twice daily (200 mg b.i.d.) and ingested without food restrictions. The drug binds to viral reverse transcriptase and blocks polymerase activity by disrupting the catalytic site (16). Consequently, nevirapine must enter cells to inhibit viral replication, and it is important to consider the intracellular drug concentration in peripheral blood mononuclear cells (PBMC) and other compartments, as the distribution of antiviral drugs from the plasma into cells and tissues is dependent on many complex factors, including affinities for cells versus plasma components or drug transporters (9, 19). As a consequence, the intracellular levels may be very different from those recorded in plasma. Knowledge of the intracellular distribution may help in understanding the mechanisms that are involved in the evolution of drug resistance and the development of sanctuary sites.Several high-performance liquid chromatographic (HPLC) assays combined with UV detection (6, 10, 22) or tandem mass spectrometry (14,24) for the quantitative determination of NVP in plasma have been described. However, these methods are characterized by a relatively high limit of quantification (10 ng ml Ϫ...

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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

Sensitive Enzyme Immunoassay for Measuring Plasma and Intracellular Nevirapine Levels in Human Immunodeficiency Virus-Infected Patients

Azoulay

Nevers

Créminon

et al. 2004

Antimicrob Agents Chemother

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“…Data were collected on standardized forms from clinical case notes and computer-based medical records. We verified the data for all pregnant patients manually using the clinical case notes.Plasma concentrations of NVP were determined using a validated high-performance liquid chromatography assay with ultraviolet detection, with a modification described previously [18]. Although a clear cut-off value (below which a statistically significant increased risk of virological failure occurs) is lacking, an increased risk of virological failure is observed when random NVP plasma concentrations are below 3.0 mg/L [16,19,20].…”

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Steady‐state nevirapine plasma concentrations are influenced by pregnancy

et al. 2008

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ObjectivesOptimal plasma concentrations of antiretroviral drugs are required during pregnancy to treat maternal HIV infection and prevent mother-to-child transmission. We investigated the effect of pregnancy on nevirapine (NVP) plasma concentrations. MethodsWe included all HIV-1-infected women for whom NVP plasma concentrations were available as part of routine patient care at two university hospitals. Plasma NVP concentrations were compared for pregnant (n 5 45) and non-pregnant (n 5 152) women. Univariate and multivariate linear regression analyses were used to identify and adjust for other confounding factors associated with NVP plasma concentrations. For pregnant women who had a plasma NVP concentration available both during and outside pregnancy, a paired analysis was performed. ResultsSteady-state NVP plasma concentrations were lower in pregnant women: 5.2 mg/L (interquartile range 3.9-6.8) vs. 5.8 mg/L (4.3-7.7) (P 5 0.08). After adjusting for confounders, both pregnancy (regression coefficient 5 -0.90 mg/L, P 5 0.046) and African descent (regression coefficient 5 11.13 mg/L, P 5 0.005) influenced NVP concentrations significantly. The paired analysis showed mean concentrations of 4.8 mg/L during pregnancy and 5.8 mg/L outside pregnancy (paired t-test, P 5 0.073). ConclusionsPregnancy has a moderate but significant lowering effect on NVP plasma concentrations. Being of African descent compensates for the lowering effect of pregnancy on NVP concentrations.Keywords: HIV-1 infection, nevirapine, plasma drug concentrations, pregnancy IntroductionThe non-nucleoside reverse transcriptase inhibitor nevirapine (NVP) is widely used for the treatment of HIV-1 infection -especially in resource-limited settings, where it is often used in low-cost fixed-dose combinations.NVP is one of the drugs that can be used safely during pregnancy as part of highly active antiretroviral therapy (HAART) [1][2][3][4]. Pregnancy itself does not seem to increase the risk of toxicity [5]. Initiating NVP treatment is no longer recommended in women with CD4 counts above 250 cells/mL. However, many women are already on a HAART regimen containing NVP when they become pregnant, and this number is increasing because of the many programmes bringing HAART to resource-limited settings.Correspondence: Dr Jeannine FJB Nellen, Academic Medical Centre, F4-217, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Tel: 1 31 20 566 4380; fax: 1 31 20 697 2286; e-mail: f.j.nellen@amc.uva.nl DOI: 10.1111/j.1468-1293.2008.00551.x HIV Medicine (2008, 9, 234-238 r 2008 British HIV Association 234Pregnancy is accompanied by a variety of physiological changes that affect pharmacokinetics [6], resulting in lower plasma concentrations for several protease inhibitors (PI) [7][8][9][10]. NVP is metabolized through the cytochrome P450 isoenzymes CYP 3A4 (56%) and CYP 2B6 (32%) [11]. The upregulation of CYP 3A4 during pregnancy and the increase in volume of distribution might lead to lower NVP plasma concentrations during pregnancy [6,12,13]. There are no data on ...

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“…The concentration of nevirapine in the plasma samples was analyzed by modified reported methods (Hollanders et al, 2000;Kabra et al, 2009;Minzi & Ngaimisi, 2010). The HPLC apparatus consisted of Jasco PU-980 Intelligent HPLC pump (Jasco, Japan) equipped with a Jasco UV-975 Intelligent UV/VIS detector (Jasco, Japan), an autosampler Jasco AS-950-10 Intelligent sample (Jasco, Japan), a Jasco Borwin chromatography software (version 1.50) integrator software and a LCGC Qualisil BDS C18 (4.6 mm Â 250 mm and 5 mm particle size) column.…”

Section: Hplc Analysismentioning

confidence: 99%

Role of lipid-based excipients and their composition on the bioavailability of antiretroviral self-emulsifying formulations

Chudasama

Patel

Nivsarkar³

et al. 2014

Drug Delivery

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The objective of this study was to develop self-emulsifying drug delivery system (SEDDS) to improve solubility and enhance the oral absorption of the poorly water-soluble drug, nevirapine. This lipid-based formulation may help to target the drug to lymphoid organs where HIV-1 virus resides mainly. The influence of the oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SEDDS were investigated in detail. Two SEDDS (F1 and F2) were prepared and characterized by morphological observation, droplet size and zeta potential determination, cloud point measurement and in vitro diffusion study. The influence of droplet size on the absorption from formulations with varying concentration of oil and surfactant was also evaluated from two self-emulsifying formulations. Oral bioavailability of nevirapine SEDDS was checked by using rat model. Results of diffusion rate and oral bioavailability of nevirapine SEDDS were compared with marketed suspension. The absorption of nevirapine from F1 and F2 showed 1.92 and 1.98-fold increase (p50.05) in relative bioavailability, respectively, compared with that of the suspension. There was no statistical significant difference (p50.05) between F1 and F2 in their AUC and C max . This indicated that there was apparent poor correlation between the droplet size and in vivo absorption. However, nevirapine in SEDDS showed higher ex vivo stomach and intestinal permeability and in vivo absorption than the marketed suspension, suggesting that the SEDDS may be a useful delivery system for targeting nevirapine to lymphoid organs.

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Determination of nevirapine, an HIV-1 non-nucleoside reverse transcriptase inhibitor, in human plasma by reversed-phase high-performance liquid chromatography

Cited by 55 publications

References 6 publications

Sensitive Enzyme Immunoassay for Measuring Plasma and Intracellular Nevirapine Levels in Human Immunodeficiency Virus-Infected Patients

Sensitive Enzyme Immunoassay for Measuring Plasma and Intracellular Nevirapine Levels in Human Immunodeficiency Virus-Infected Patients

Steady‐state nevirapine plasma concentrations are influenced by pregnancy

Role of lipid-based excipients and their composition on the bioavailability of antiretroviral self-emulsifying formulations

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