Use of dried blood spots for the determination of plasma concentrations of nevirapine and efavirenz

Kromdijk, Wiete; Mulder, J.; Rosing, Hilde; Smit, Patrick M.; Beijnen, Jos H.; Huitema, Alwin D. R.

doi:10.1093/jac/dks011

Cited by 53 publications

(53 citation statements)

References 14 publications

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“…The samples were stored at −20°C and shipped on dry ice, in zip lock bags with a desiccant packet in each bag and considered stable. 45 Time of the last ARV dose was determined per parent/guardian-report. DBS samples from Ugandan children were analyzed for EFV, LPV and NVP using a validated liquid chromatography-mass spectrometry method as described previously with similar assay conditions for NVP; 46 lower limits of quantification (LLOQ) for EFV, LPV and NVP were 0.1 mg/L, 0.01 mg/L and 0.01 mg/L, respectively.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-infected Children in Tororo, Uganda

Bartelink¹,

Savic

Dorsey³

et al. 2015

Pediatric Infectious Disease Journal

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Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (P<0.001) with a trend towards greater bioavailability when malnourished. Children receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z-scores were associated with reduced risk of virologic failure (p=0.034, p=0.068 respectively). Conclusions Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children.

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Section: Methodsmentioning

confidence: 99%

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-infected Children in Tororo, Uganda

Bartelink¹,

Savic

Dorsey³

et al. 2015

Pediatric Infectious Disease Journal

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“…Over the last decade, a rising number of DBS assays for different classes of drugs have been reported. So far, antidiabetics, immunosuppressants, analgesics, anti-HIV drugs, antihypertensive drugs, antimicrobial agents, anti-epileptics, and the iron chelator deferasirox have been included [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Among the antidepressants, a DBS assay for analysis of IMP has previously been described as well as for the SSRIs fluoxetine, reboxetine, and paroxetine, and for the atypical antidepressant venlafaxine [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

A simple dried blood spot method for therapeutic drug monitoring of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their active metabolites using LC-MS/MS

Berm

Paardekooper

Brummel-Mulder

et al. 2015

Talanta

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“…DBS analysis for TDM has been demonstrated previously for other drugs used in infectious diseases, such as anti-HIV, antimalaria, and antituberculosis drugs (27)(28)(29)(30). DBS analysis has several advantages, including a less-invasive sampling procedure, a smaller sampling volume, simpler storage and transfer of samples at room temperature, and no biohazard risk during the shipment of samples (31)(32)(33).…”

mentioning

confidence: 99%

Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

Elst

Span

Hateren

et al. 2013

Antimicrob Agents Chemother

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e Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P ‫؍‬ 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

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Use of dried blood spots for the determination of plasma concentrations of nevirapine and efavirenz

Abstract: Dried blood spot concentrations of nevirapine and efavirenz were equal to plasma concentrations after correction for haematocrit and compound-specific plasma protein binding and can therefore be used in clinical practice.

Cited by 53 publications

References 14 publications

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-infected Children in Tororo, Uganda

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-infected Children in Tororo, Uganda

A simple dried blood spot method for therapeutic drug monitoring of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their active metabolites using LC-MS/MS

Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

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