title: Estimating systemic exposure to levonorgestrel from an oral contraceptive.
abstract: OBJECTIVE
  The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC.
  
  
  METHODS
  We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes.
  
  
  RESULTS
  The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively].
  
  
  CONCLUSIONS
  Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects.
  
  
  CONCLUSIONS
  A single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting.
authors.affiliation: Department of Obstetrics and Gynecology and Epidemiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Cale N
authors.initials: CN
authors.lastname: Basaraba
authors.affiliation: Department of Obstetrics and Gynecology and Epidemiology, Columbia University Medical Center, New York, NY, USA. Electronic address: clw3@columbia.edu.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: Nandakumar
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, USA; Departments of Pathology and Cell Biology, and Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D003271:Contraceptive Agents, Female / Q000493:pharmacokinetics*; D004967:Estrogens; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000493:pharmacokinetics*; D011372:Progestins; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014156:Transcortin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D004967:Estrogens; D011372:Progestins; D012738:Sex Hormone-Binding Globulin; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D014156:Transcortin
keywords: Ethinyl estradiol; Levonorgestrel; Oral contraceptives; Pharmacokinetics; Single dose; Steady state