Simultaneous Determination of the HIV Drugs Indinavir, Amprenavir, Saquinavir, Ritonavir, Lopinavir, Nelfinavir, the Nelfinavir Hydroxymetabolite M8, and Nevirapine in Human Plasma by Reversed-Phase High-Performance Liquid Chromatography

Droste, Jacqueline A. H.; Wissen, C.P.W.G.M. Verwey-van; Burger, David M.

doi:10.1097/00007691-200306000-00023

Cited by 125 publications

(77 citation statements)

References 15 publications

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“…Plasma was separated and stored at Ϫ80°C until assayed. LPV concentrations were measured by a high-performance liquid chromatography assay using a UV detector, according to a validated method (24), with accuracy and precision of 100% Ϯ 15% and Ͻ10%, respectively. The assay was linear over the range of 0.08 to 10 g/ml for plasma concentrations and validated for a concentration range of 0.123 to 10 g/ml.…”

Section: Methodsmentioning

confidence: 99%

Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

López‐Cortés

Ruiz-Valderas

Sánchez-Rivas

et al. 2013

Antimicrob Agents Chemother

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There is significant intra-and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI 95 There is significant controversy regarding ritonavir-boosted protease inhibitor (PI) monotherapy as a maintenance therapeutic strategy (1-5). Notwithstanding, a considerable proportion of patients maintained an undetectable viremia on lopinavirritonavir maintenance monotherapy (mtLPVr) and could benefit from a simpler regimen without nucleoside analogues or other antiretroviral drugs. Moreover, lack of adherence has been indicated as the main reason for virological failure (VF) in different studies (6-13).Moreover, there is significant intra-and intersubject variability in LPV plasma concentrations after standard dosing, determined largely by variability in drug absorption, cytochrome P450 metabolism, plasma protein binding, and drug transporter activity, which may affect the disposition of the drug (14, 15). As LPV plasma concentrations and the genotype inhibitory quotient have been related to virological efficacy in experienced patients on LPVr-based regimens (16)(17)(18)(19), in this study, we tested whether low plasma LPV trough concentrations contribute to VF throughout the mtLPVr treatment period. The confirmation of this hypothesis would demonstrate that LPV therapeutic drug monitoring could be useful in improving the efficacy of LPV when prescribed as a monotherapy. MATERIALS AND METHODSStudy population and design. From April 2009 to April 2010, adult HIV-1-infected patients who started a regimen of mtLPVr at our outpatient clinic were consecutively included in this observational, prospective, open-label study. The LPVr dosing regimen (400 mg of LPV and 100 mg of ritonavir twice daily or 800 mg-200 mg once daily) was selected by the patients' physicians. All subjects had plasma HIV RNA levels of Ͻ50 copies/ml for at least 6 months. Patients with VF while on a PI-containing regimen were also included in the study when genotypic resistance tests showed no major or Յ3 minor resistance mutations associated with reduced...

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Section: Methodsmentioning

confidence: 99%

Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

López‐Cortés

Ruiz-Valderas

Sánchez-Rivas

et al. 2013

Antimicrob Agents Chemother

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“…Plasma samples were analyzed for amprenavir, ritonavir, and paroxetine (total concentrations) at the Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre. The Department of Clinical Pharmacy has established a high-pressure liquid chromatography (HPLC) assay for amprenavir and ritonavir, derived from a reversed-phase HPLC method which was published previously (10). The method involves liquid-liquid extraction from plasma, followed by HPLC with an OmniSpher 3 C 18 column (100 by 4.6 mm) and UV detection at 215 nm.…”

Section: Study Design and Dosing Of Study Drugsmentioning

confidence: 99%

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Lee

Blenke

Rongen

et al. 2007

Antimicrob Agents Chemother

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Human immunodeficiency virus-infected patients have an increased risk for depression. Despite the high potential for drug-drug interactions, limited data on the combined use of antidepressants and antiretrovirals are available. Theoretically, ritonavir-boosted protease inhibitors may inhibit CYP2D6-mediated metabolism of paroxetine. We wanted to determine the effect of fosamprenavir-ritonavir on paroxetine pharmacokinetics and vice versa and to evaluate the safety of the combination. Group A started with 20 mg paroxetine every day for 10 days; after a wash-out period of 16 days, subjects received paroxetine (20 mg every day) plus fosamprenavir-ritonavir (700/100 mg twice a day) from days 28 to 37. Group B received the regimens in reverse order. On days 10 and 37, pharmacokinetic curves were recorded. Twenty-six healthy subjects ( t 1/2 ). The free fraction of paroxetine showed a median (interquartile range) increase of 30% (18 to 42%) after the addition of fosamprenavir-ritonavir. The AUC 0-12 , C max , C min , and t 1/2 of amprenavir and ritonavir were similar to those of historical controls. No serious adverse events occurred. Fosamprenavirritonavir reduced total paroxetine exposure by 55%. This is partly explained by protein displacement of paroxetine. We think that this interaction is clinically relevant and that titration to a higher dose of paroxetine may be necessary to accomplish the needed antidepressant effect.

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“…The lower limit of quantification is 0.07 mg/L. Average accuracy ranged from 97% -106% and precision ranged from 2.4% -8.1%, with inter-assay coefficient of variation 2.3% -5.9% [13].…”

Section: Measurement Of Lopinavir Drug Concentrationsmentioning

confidence: 93%

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

Hofstede¹,

Koopmans²,

Burger³

et al. 2012

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Antiretroviral therapy in HIV patients is known for its negative effect on the cardiovascular system. One of the major adverse events in patients on lopinavir is increasing lipids. Hyperlipidaemia together with chronic inflammation by HIV-infection itself makes these patients prone for cardiovascular diseases.The purpose of this study (a sub study within the FREE-study) was to determine if higher plasma lopinavir (LPV) concentrations lead to increase of serum lipids. Plasma drug concentrations were analysed up to week 24 in a prospective cohort of HIV antiretroviral therapy naive patients who started on a regimen of zidovudine, lamivudine and ritonavir-boosted lopinavir (FREE study). Prospectively we measured plasma lopinavir concentrations from baseline to week 24 in 72 naive HIV-patients starting on lopinavir (59 males and 13 females). A total of 210 samples were analysed, with at least 2 samples in every patient. Mean LPV trough concentration was 4.3 mg/L (± 2.1). The median intra-subject variation in LPV level was 38% (range 4% -111%). Serum lipids were not correlated to LPV plasma concentrations possibly due to the wide intra-individual variability in LPV trough levels. Monitoring of plasma lopinavir and subsequent dose adjustment of LPV will not be useful to prevent hyperlipidaemia in HIV-patients treated with lopinavir.

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Simultaneous Determination of the HIV Drugs Indinavir, Amprenavir, Saquinavir, Ritonavir, Lopinavir, Nelfinavir, the Nelfinavir Hydroxymetabolite M8, and Nevirapine in Human Plasma by Reversed-Phase High-Performance Liquid Chromatography

Cited by 125 publications

References 15 publications

Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

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Simultaneous Determination of the HIV Drugs Indinavir, Amprenavir, Saquinavir, Ritonavir, Lopinavir, Nelfinavir, the Nelfinavir Hydroxymetabolite M8, and Nevirapine in Human Plasma by Reversed-Phase High-Performance Liquid Chromatography

Cited by 125 publications

References 15 publications

Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Na&#239;ve HIV-Patients: A Sub Analysis of the FREE Study

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Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study