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As acetaminophen plasma and CSF levels are linearly dose proportional,18,19 individual concentration results from the 1,300?mg PR dose were standardized to 1,000?mg to facilitate comparison with data from IV and PO routes. Mean concentration-time profiles also were generated for each route of administration. The following PK AZ191 parameters for both plasma and CSF were generated: mean maximum concentration (Cmax/CSFmax), median time to maximal concentration (Tmax), mean elimination half-life (t?), and mean area under the curve from T0 to 6?hours (AUC0�C6). MedTox Laboratories, Inc. (St Paul, MN, U.S.A.) performed the plasma acetaminophen assays, and iC42 Integrated Solutions in Systems Biology for Clinical Research & Development (Aurora, CO, U.S.A.) Apoptosis Compound Library ic50 performed the CSF assays. Both companies used validated analytical LC/MS/MS methods to generate acetaminophen concentration values. Pharsight, a Certara? Company, generated the mean concentration-time curves and conducted the noncompartmental PK analyses. The mean differences in PK parameters from each route of administration were compared using a paired t-test. Five Caucasian and 2 African-American men with a mean (range) age of 29.4 (19 to 44) years were enrolled. All subjects met eligibility criteria with the exception of 2 subjects given a waiver for BMIs of 25.3 and 25.6. Each subject had an unremarkable medical history, was afebrile, and had normal vital signs and physical examinations on clinic admission. One subject was discontinued from study participation and replaced because of premature failure of his spinal catheter on day 2 after post PO PK assessments were completed; however, his results from day 1 PO dosing were included in the final PK results (Table?1). One subject in the PR group had missing CSF samples and was therefore excluded from the analysis (Table?2). The plasma PK results are presented in Table?1, and the CSF results are presented Wnt inhibitor in Table?2. Note that to standardize the PR dose to 1,000?mg, individual concentration values at each time point were adjusted to create standardized concentration-time curves, and these individual values were used to calculate mean PK parameters. After an IV, PO, or PR 1,000?mg acetaminophen dose, the mean plasma Cmax values were 21.6, 12.3, and 6.1?��g/mL, respectively (Table?1). The IV route produced a 76% or 256% higher Cmax than the PO (P?=?0.0004) or PR (P?
