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Table 1.

Cynomolgus dosing and administration route groups.

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Fig 1.

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

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

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Fig 1 Expand

Table 2.

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

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Table 2 Expand

Fig 2.

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

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

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Fig 2 Expand

Table 3.

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

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Table 3 Expand

Table 4.

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

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Table 4 Expand

Fig 3.

Proportional relationship between idursulfase-IT dose and CSF I2S AUCinf and Cmax.

AUCinf, area under the serum concentration-time curve extrapolated to infinity; Cmax, maximum observed concentration; CSF, cerebrospinal fluid; I2S, iduronate-2-sulfatase.

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Fig 3 Expand

Fig 4.

Mean CSF I2S concentration-time profiles.

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.

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Fig 4 Expand

Table 5.

Bioavailability and exposure fraction (AUCinf) of I2S in the serum and CSF after IT-L dosing.

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Table 5 Expand