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Optimal multi‐drug PK sampling strategies (OSS) for efavirenz (EFV) & indinavir (IDV)
Author(s) -
Ma Q.,
Forrest A.,
Rosenkranz S.,
Para M. F.,
Adams E.,
Yarasheski K. E.,
Reichman R. C.,
Morse G. D.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.052
Subject(s) - efavirenz , indinavir , pharmacology , human immunodeficiency virus (hiv) , drug , clinical pharmacology , sampling (signal processing) , pharmacokinetics , medicine , amprenavir , antiretroviral therapy , viral load , computer science , virology , chemistry , protease , biochemistry , filter (signal processing) , hiv 1 protease , computer vision , enzyme
Aims Intensive sampling strategies (ISS) are not feasible in many patient populations. Methods to design sparse OSS have not been adequately described for multi‐drug regimens. The objective of the present study was to develop a sparse efficient multi‐drug OSS for evaluation of PK in patients receiving antiretroviral (ARV) regimens. Methods Two OSS with 4 or 6 sampling times (OSS4, OSS6) constrained to 8h post‐dose at steady state were computed using D‐optimality (ADAPT II). These OSS were developed based on 'intensive' steady state PK data modeled using ADAPT II from 14 healthy volunteers in ACTG A5043 given EFV, IDV and amprenavir. Bias and precision of OSS estimates of clearance (CL), compared to estimates based on the ISS, were determined. Results OSS4 had samples at pre, 2, 5 and 8h post‐dose; OSS6 added 1 and 4h samples. For both of the OSS, CL estimates were unbiased. Mean absolute errors for EFV were 5.6 and 3.9% and for IDV were 15.8 and 4.1%, for OSS4 and OSS6, respectively. Conclusion This approach to designing sparse OSS will facilitate PK/PD studies in patient populations receiving multi‐drug ARV regimens. Clinical Pharmacology & Therapeutics (2005) 77 , P42–P42; doi: 10.1016/j.clpt.2004.12.052