Document 0112
 DOCN  M9550112
 TI    Interspecies scaling and pharmacokinetic parameters of 3TC in humans.
 DT    9505
 AU    Hussey EK; Donn KH; Daniel MJ; Hall ST; Harker AJ; Evans GL; Glaxo Inc.
       Research Institute, Research Triangle Park, North; Carolina 27709.
 SO    J Clin Pharmacol. 1994 Oct;34(10):975-7. Unique Identifier : AIDSLINE
       MED/95138293
 AB    3TC is a dideoxy-nucleoside analogue that has demonstrated in-vitro
       activity against human immunodeficiency virus (HIV). 3TC concentrations
       in humans were predicted before the initiation of clinical trials by
       interspecies scaling of pharmacokinetic parameters observed in animal
       species. Clearance and volume of distribution were estimated for humans
       using linear regression on a log-log scale of each parameter versus body
       weight for rats and dogs. The concentration-time profile and the average
       serum concentration at steady state after various dosage regimens were
       estimated as a basis for initial dose selection for clinical trials. The
       predicted parameters (clearance of 16.3 L/hr and volume of distribution
       of 40 L for a 70-kg man) were compared with that observed (mean
       clearance of 24 L/hr and mean volume of distribution of 96 L, mean
       weight of 74 kg) in 20 asymptomatic, HIV positive, volunteers after
       single intravenous doses of 3TC. Interspecies scaling was applied
       prospectively as a rationale for dose selection of 3TC in clinical
       trials.
 DE    Animal  Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS  Body
       Weight/PHYSIOLOGY  Comparative Study  Cross-Over Studies
       Cytosine/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/
       PHARMACOKINETICS  Dogs  Human  HIV Seropositivity/METABOLISM  Infusions,
       Intravenous  Male  Rats  Reverse Transcriptase/*ANTAGONISTS & INHIB
       Species Specificity  CLINICAL TRIAL  JOURNAL ARTICLE

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