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Nelfinavir (NFV) population pharmacokinetics (PK) in long‐term suppressors compared with the pk of the new 625 mg formulation in healthy volunteers
Author(s) -
Capparelli E.,
Goebel F. D.,
Williams I.,
Opravil M.,
Nelson M.,
Daniels E.,
Pun E.,
Hsyu P.
Publication year - 2004
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.2003.11.121
Subject(s) - nelfinavir , pharmacokinetics , pharmacology , population , medicine , nonmem , network functions virtualization , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , immunology , environmental health , cloud computing , computer science , operating system
Background We determined the NFV (250 mg tablet) AUC in patients who maintained undetectable HIV RNA for >72 weeks to understand the exposure of NFV in long‐term responders. In addition, the exposure was compared to that from a new NFV formulation (625 mg tablet) to determine how well the new formulation achieves concentrations associated with maximal long‐term HIV suppression. Methods Patients receiving NFV in combination with 2 NRTI's with HIV suppression (<50 copies/mL) for > 72 weeks were enrolled. PK samples were collected after observed doses of NFV (5 × 250mg tablets) BID. 46 subjects with PK samples contributed 225 levels to this analysis. NONMEM was used to construct a population pharmacokinetic model for NFV. Individual AUC 0–12 was estimated and compared to NFV AUC observed in a separate phase PK study of 14 healthy subjects taking 2 × 625mg NFV tablet BID. Results The median CL/F and AUC 0–12 were 53.7 L/hr and AUC was 23.3 mcg*hr/mL (range = 7.8‐49), respectively. This NFV exposure is consistent with prior studies. NFV AUC following administration of the 625mg formulation was approximately double (median [range] = 48 [18.6‐74.2] mcg*hr/mL) the exposure seen in long‐term suppressors (250mg tablets). Conclusions Long term HIV suppression with NFV was achieved with typical NFV exposures. Initial PK of the new 625 mg tablet in healthy volunteers resulted in NFV exposures greater than that observed in long‐term suppression. Clinical Pharmacology & Therapeutics (2004) 75 , P32–P32; doi: 10.1016/j.clpt.2003.11.121