title: Evaluation of effect of impaired renal function on lamivudine pharmacokinetics.
abstract: OBJECTIVE
  This study aimed to describe lamivudine pharmacokinetics in patients with impaired renal function and to evaluate the consistency of current dosing recommendations.
  
  
  METHODS
  A total of 244 patients, ranging in age from 18 to 79 years (median 40 years) and in bodyweight from 38 to 117 kg (median 71 kg), with 344 lamivudine plasma concentrations, were analysed using a population pharmacokinetic analysis. Serum creatinine clearance (CLCR) was calculated using the Cockcroft-Gault formula; 177 patients had normal renal function (CLCR > 90 ml min(-1) ), 50 patients had mild renal impairment (CLCR = 60-90 ml min(-1) ), 20 patients had moderate renal impairment (CLCR = 30-60 ml min(-1) ), and five patients had severe renal impairment (CLCR < 30 ml min(-1) ).
  
  
  RESULTS
  A two-compartment model adequately described the data. Typical population estimates (percentage interindividual variability) of the apparent clearance (CL/F), central (Vc /F) and peripheral volumes of distribution (Vp /F), intercompartmental clearance (Q/F) and absorption rate constant (Ka ) were 29.7 l h(-1) (32%), 68.2 l, 114 l, 10.1 l h(-1) (85%) and 1 h(-1) , respectively. Clearance increased significantly and gradually with CLCR. Our simulations showed that a dose of 300 mg day(-1) in patients with mild renal impairment could overexpose them. A dose of 200 mg day(-1) maintained an exposure close to that of adults with normal renal function. However, the current US Food and Drug Administration recommendations for lamivudine in other categories of patients (from severe to moderate renal impairment) provided optimal exposures.
  
  
  CONCLUSIONS
  Lamivudine elimination clearance is related to renal function. To provide optimal exposure, patients with mild renal impairment should receive 200 mg day(-1) instead of 300 mg day(-1) .
authors.affiliation: EA 3620, Université Paris Descartes Sorbonne Paris Cité, Paris, France; Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France.
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Viard
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D019259:Lamivudine / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine
keywords: human immunodeficiency virus; lamivudine; population pharmacokinetics; renal impairment
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