Practical Guidelines to Interpret Plasma Concentrations of Antiretroviral Drugs

Kappelhoff, Bregt S; Huitema, Alwin D. R.; Beijnen, Jos H.

doi:10.2165/00003088-200544040-00009

Cited by 24 publications

(36 citation statements)

References 3 publications

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“…Nevirapine concentrations below 3 mg/L increase the risk of virological failure by fivefold [7], and dose adjustment has been suggested if nevirapine C min is lower than 3 mg/L or higher than 12 mg/L [22,23]. Our results show that nevirapine concentrations following twice daily doses of nevirapine 200 mg can be lower than the recommended 3 mg/L when taken concomitantly with rifampicin (Fig.…”

Section: Discussionmentioning

confidence: 65%

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

Elsherbiny

Cohen

Jansson

et al. 2008

Eur J Clin Pharmacol

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Section: Discussionmentioning

confidence: 65%

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

Elsherbiny

Cohen

Jansson

et al. 2008

Eur J Clin Pharmacol

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“…ICs measured in vitro must be adjusted for protein binding before extrapolation to the clinical setting. Moreover, ICs suffer from variability due to a lack of standardization of phenotyping methods (14). There are three methods for adjusting the in vitro IC for protein binding, namely, multiplication of the IC by the free fraction measured in vivo, measurement of the IC in the presence of 50% human serum albumin, and multiplication of the IC by a constant to adjust for assay variations (20), but none of these methods has been clinically validated.…”

Section: Discussionmentioning

confidence: 99%

Predictive Values of the Human Immunodeficiency Virus Phenotype and Genotype and of Amprenavir and Lopinavir Inhibitory Quotients in Heavily Pretreated Patients on a Ritonavir-Boosted Dual-Protease-Inhibitor Regimen

Barrail-Tran

Morand‐Joubert

Poizat

et al. 2008

Antimicrob Agents Chemother

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“…Estimates of drug exposure (AUC from time zero to 12 h [AUC 0 -12 ]) and the apparent elimination half-life (t 1/2 ) over 12 h were calculated using noncompartmental analysis (WinNonlin software, version 6.1; Pharsight Corporation, Mountain View, CA). The MEC for LPV in treatment-naive patients was defined to be 1,000 ng/ml, as this was previously found to be associated with a high response rate in nonpregnant and treatment-naive adults with wild-type HIV-1 infection (16,21). Intra-and interindividual variabilities in pharmacokinetic parameters were expressed in terms of the percent CV.…”

Section: Methodsmentioning

confidence: 99%

“…The study authors recommended increasing the dose of LPV/r during the third trimester. Others, however, argued against such a global recommendation since plasma LPV concentrations at standard dosing were often above the accepted minimum effective concentration (MEC; 1,000 ng/ml) for treatment of naive patients (16,21). Furthermore, there was considerable interpatient variability and no evidence that efficacy was compromised with reduced plasma LPV exposure in the third trimester.…”

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confidence: 99%

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Else

Douglas

Dickinson

et al. 2012

Antimicrob Agents Chemother

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Lopinavir exposure was reduced during the third trimester in pregnant women receiving standard dosing of the soft-gel capsule (SGC; 400/100 mg twice daily [b.i.d.]). Pharmacokinetic data on the lopinavir tablet in pregnancy are limited. On the basis of the tablet's improved bioavailability, standard dosing (400/100 mg b.i.d.) may provide adequate lopinavir exposure in pregnancy without a need for dose adjustment. Here we compared the total and unbound lopinavir pharmacokinetics throughout pregnancy in the second and third trimesters in HIV-infected women receiving standard dosing of the lopinavir SGC or tablet. Postpartum sampling was also performed in patients continuing therapy postdelivery. Blood samples were collected at 0 to 12 h postdosing, and lopinavir concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry. Nineteen patients were included: 8 received the SGC (cohort 1) and 11 received the tablet (cohort 2). Total lopinavir exposures in the third trimester were lower than those in the second trimester (35 and 28% for cohorts 1 and 2, respectively) and postpartum (35% for cohort 2). In the third trimester, the area under the concentration-time curve (AUC) from 0 to 12 h (AUC 0 -12 ) and maximum concentration were ϳ15% and 25% higher, respectively, for the lopinavir tablet than the SGC. One SGC patient had lopinavir concentrations of <1,000 ng/ml; all patients on the tablet had concentrations of >1,000 ng/ml. In cohort 2, the percentage of the AUC that was unbound was higher (nonsignificantly) in the second (1.28%) and third (1.18%) trimesters than postpartum (1.01%). Seventeen of 19 patients had an undetectable viral load at delivery. There were no HIV transmissions. Although lopinavir (tablet) exposures were reduced during the third trimester, the higher total and unbound concentrations achieved in women receiving the tablet than in women receiving the SGC suggest that the tablet's improved oral bioavailability may partly compensate for the reduction in lopinavir exposure during the later stages of pregnancy.A ntiretroviral therapies (ARTs), with the exception of zidovudine, are unlicensed for use in pregnancy. However, they are widely used, in accordance with national and international guidelines, both for maternal treatment and for the prevention of HIV mother-to-child transmission (MTCT). Multiple physiological changes which can impact the pharmacokinetics (PKs) of these agents occur during pregnancy; therefore, studies in pregnancy are required to ensure appropriate dosing and avoid unnecessary toxicity or treatment failure. Protease inhibitors (PIs) are widely used during pregnancy for both treatment and prevention of MTCT due to their efficacy, lack of CD4 count-dependent toxicity, and short half-lives (t 1/2 s). However, plasma concentrations of certain protease inhibitors have repeatedly been shown to be significantly reduced during the third trimester, with some concerns over efficacy (37).Lopinavir (LPV)-ritonavir (RTV), or LPV/r, is used during pregnancy,...

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Practical Guidelines to Interpret Plasma Concentrations of Antiretroviral Drugs

Cited by 24 publications

References 3 publications

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

Predictive Values of the Human Immunodeficiency Virus Phenotype and Genotype and of Amprenavir and Lopinavir Inhibitory Quotients in Heavily Pretreated Patients on a Ritonavir-Boosted Dual-Protease-Inhibitor Regimen

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

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