Comparisons of serum I2S pharmacokinetic parameters after 4 different idursulfase treatments.

<p><i>AUC</i>_inf, area under the concentration-time curve extrapolated to infinity; <i>AUC</i>_0-t, area under the concentration-time curve from time 0 to the last sampling time; CL, total clearance; <i>C</i>_max, maximum observed concentration; I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar; IV, intravenous; <i>MRT</i>_inf, mean residual time derived from time 0 to infinity; na, not available; SD, standard deviation; <i>t</i>_½, terminal half-life; <i>T</i>_max, time of occurrence of <i>C</i>_max; <i>V</i>_ss, volume of distribution at steady state; <i>V</i>_z, volume of distribution during terminal phase; λ_Z, apparent terminal rate constant.</p><p>^aUnits were ml/kg for IV dosing and ml for IT-L</p><p>^bn = 6</p><p>^cn = 7</p><p>^dUnits were ml/h/kg for IV dosing and ml/h for IT-L.</p><p>Comparisons of serum I2S pharmacokinetic parameters after 4 different idursulfase treatments.</p

CSF pharmacokinetic parameters of idursulfase IV and IT at lumbar level.

<p><i>AUC</i>_inf, area under the concentration-time curve extrapolated to infinity; <i>AUC</i>_0-t, area under the concentration-time curve from time 0 to the last sampling time; CL, total clearance; <i>C</i>_max, maximum observed concentration; CSF, cerebrospinal fluid; I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar; IV, intravenous; <i>MRT</i>_inf, mean residual time derived from time 0 to infinity; na, not available; <i>t</i>_½, terminal half-life; <i>T</i>_max, time of occurrence of <i>C</i>_max; <i>V</i>_ss, volume of distribution at steady state; <i>V</i>_z, volume of distribution during terminal phase; λ_Z, apparent terminal rate constant.</p><p>^aUnits were ml/kg for IV and ml for IT-L dosing</p><p>^bUnits were ml/h/kg for IV dosing and ml/h for IT-L.</p><p>CSF pharmacokinetic parameters of idursulfase IV and IT at lumbar level.</p

CSF pharmacokinetic parameters of idursulfase IV and IT at CM level.

<p><i>AUC</i>_inf, area under the concentration-time curve extrapolated to infinity; <i>AUC</i>_0-t, area under the concentration-time curve from time 0 to the last sampling time; CL, total clearance; CM, cisterna magna; <i>C</i>_max, maximum observed concentration; CSF, cerebrospinal fluid; I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar; IV, intravenous; <i>MRT</i>_inf, mean residual time derived from time 0 to infinity; na, not available; SD, standard deviation; <i>t</i>_½, terminal half-life; <i>T</i>_max, time of occurrence of <i>C</i>_max; <i>V</i>_ss, volume of distribution at steady state; <i>V</i>_z, volume of distribution during terminal phase; λ_Z, apparent terminal rate constant.</p><p>^aUnits were ml/kg for IV and ml for IT-L dosing</p><p>^bn = 3</p><p>^cUnits were ml/h/kg for IV dosing and ml/h for IT-L.</p><p>CSF pharmacokinetic parameters of idursulfase IV and IT at CM level.</p

Mean CSF I2S concentration-time profiles.

<p>After intravenous and IT-L dosing, mean CSF I2S concentration-time profiles were determinedwith CSF sampled at the CM level (A) and at the IT-L level (B). Error bars represent standard deviation. CSF, cerebrospinal fluid; I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar; IV, intravenous.</p

Cynomolgus dosing and administration route groups.

<p>IT-L, intrathecal lumbar; IV, intravenous, SD, standard deviation.</p><p>Cynomolgus dosing and administration route groups.</p

Proportional relationship between idursulfase-IT dose and CSF I2S <i>AUC</i>_inf and <i>C</i>_max.

<p><i>AUC</i>_inf, area under the serum concentration-time curve extrapolated to infinity; <i>C</i>_max, maximum observed concentration; CSF, cerebrospinal fluid; I2S, iduronate-2-sulfatase.</p

Mean serum and CSF I2S concentration-time profiles with 0.5 mg/kg idursulfase intravenous dose.

<p>Error bars represent standard deviation.CM, cisterna magna; CSF, cerebrospinal fluid; I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar.</p

Mean intravenous and IT-L serum I2S concentration-time profiles.

<p>Error bars represent standard deviation.I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar; IV, intravenous.</p

Bioavailability and exposure fraction (<i>AUC</i>_inf) of I2S in the serum and CSF after IT-L dosing.

<p><i>AUC</i>_inf, area under the concentration-time curve extrapolated to infinity; CM, cisterna magna; CSF, cerebrospinal fluid; EF, exposure fraction; F, bioavailability; I2S, iduronate-2-sulfatase; IT-L, intrathecal lumbar; IV, intravenous.</p><p>^aMean body weights were calculated from the animals whose CSF samples were collected at the CM level.</p><p>^bSampled at CM level.</p><p>Bioavailability and exposure fraction (<i>AUC</i>_inf) of I2S in the serum and CSF after IT-L dosing.</p