title: Clinical evaluation of the determination of plasma concentrations of darunavir, etravirine, raltegravir and ritonavir in dried blood spot samples.
abstract: BACKGROUND
  Measurement of drug levels in plasma is currently the gold standard for pharmacological studies. However, venous sampling is not feasible in some populations (e.g., neonates) or may be difficult in certain situations, such as nonhospital-based settings. Dried blood spots (DBS) can be obtained by a simple fingerprick and the subsequent collection of blood on a filter card, allowing patient-friendly sample collection in non-hospital-based settings. Despite these advantages, thus far no clinical evaluation has been performed for the use of DBS concentrations as surrogates for plasma levels. Our purpose was to clinically evaluate DBS sampling for the determination of plasma concentrations for the novel antiretroviral drugs etravirine, darunavir/ritonavir and raltegravir.
  
  
  RESULTS
  DBS concentrations were measured in 11 HIV-infected patients using LC-MS/MS. DBS concentrations were proportional to plasma concentrations. All drug concentrations were higher in DBS than in plasma samples. The plasma:DBS ratio and the respective relative standard error of estimate (RSE) of darunavir, etravirine, raltegravir and ritonavir were 0.632 (4.97% RSE), 0.523 (4.84% RSE), 0.617 (14.9% RSE) and 0.592 (2.99% RSE), respectively. Hematocrit did not explain variability in our study.
  
  
  CONCLUSIONS
  DBS are reproducibly correlated to plasma levels and can be used for monitoring antiretroviral drug exposure in HIV-infected patients.
authors.affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital, Louwesweg, Amsterdam, The Netherlands. rob@terheine.nl
authors.forename: Rob
authors.initials: R
authors.lastname: Ter Heine
authors.forename: Jan W
authors.initials: JW
authors.lastname: Mulder
authors.forename: Eric Cm
authors.initials: EC
authors.lastname: van Gorp
authors.forename: Jiri Fp
authors.initials: JF
authors.lastname: Wagenaar
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Alwin Dr
authors.initials: AD
authors.lastname: Huitema
mesh_terms: D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000069454:Darunavir; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000097:blood / Q000627:therapeutic use; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000097:blood / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000097:blood / Q000627:therapeutic use; D013449:Sulfonamides / Q000097:blood / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D013449:Sulfonamides; C451734:etravirine; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir