Clinical Pharmacokinetics of Telbivudine (LdT) in Patients with Impaired Hepatic or Renal Function

[Guest guest]

Clinical Pharmacokinetics of Telbivudine (LdT) in Patients with Impaired

Hepatic or Renal Function

Telbivudine (LdT) is a L-nucleoside with potent anti-HBV activity. This drug

is currently being studied in clinical trials in patients with chronic

hepatitis B, with compensated and decompensated liver function. LdT is

predominantly eliminated via renal clearance as unchanged drug with minimal

hepatic elimination.

The hepatic impairment study enrolled 24 subjects with normal (n=6) and

impaired hepatic function (child-Pugh Score 5-6, 7-9 and 10-15,

n=6/category).

Subjects received a single dose of 600 mg LdT.

The renal impairment study enrolled 29 subjects with normal (creatinine

clearance (CLCR) > 80 ml/min, n=8) and impaired renal function (Mild: CLCR

50-80 ml/min, n=8; Moderate: 30-49 ml/min, n=7; Severe: < 29 ml/min, n=6).

Subjects received a reduced dose as renal function decreases.

Results

LdT exhibited comparable pharmacokinetic profiles with respect to parameters

underlying peak (Cmax) and overall drug exposure (AUC) in subjects with

normal

and impaired hepatic function. However, plasma exposure of LdT is renal

function dependent.

Subjects with mild, moderate and severe renal impairment treated with a

single

dose of 600, 400 and 200 mg LdT, respectively, had comparable overall plasma

exposure to normal subjects treated with 600 mg LdT.

<graph>

Conclusion

LdT is well tolerated in all subjects. While no dose modification is

necessary

in patients with hepatic impairment, dose adjustment is recommended for

subjects with moderate or severe renal impairment by reducing LdT daily

dose.

Idenix Pharmaceuticals, Inc, Cambridge MA, USA.

04/21/04

Reference

XJ Zhou and others. CLINICAL PHARMACOKINETICS OF TELBIVUDINE, A POTENT

ANTIVIRAL FOR HEPATITIS B, IN SUBJECTS WITH IMPAIRED HEPATIC OR RENAL

FUNCTION. Abstract 452. 39th EASL. April 14-18, 2004. Berlin, Germany.

[Guest guest]

Clinical Pharmacokinetics of Telbivudine (LdT) in Patients with Impaired

Hepatic or Renal Function

Telbivudine (LdT) is a L-nucleoside with potent anti-HBV activity. This drug

is currently being studied in clinical trials in patients with chronic

hepatitis B, with compensated and decompensated liver function. LdT is

predominantly eliminated via renal clearance as unchanged drug with minimal

hepatic elimination.

The hepatic impairment study enrolled 24 subjects with normal (n=6) and

impaired hepatic function (child-Pugh Score 5-6, 7-9 and 10-15,

n=6/category).

Subjects received a single dose of 600 mg LdT.

The renal impairment study enrolled 29 subjects with normal (creatinine

clearance (CLCR) > 80 ml/min, n=8) and impaired renal function (Mild: CLCR

50-80 ml/min, n=8; Moderate: 30-49 ml/min, n=7; Severe: < 29 ml/min, n=6).

Subjects received a reduced dose as renal function decreases.

Results

LdT exhibited comparable pharmacokinetic profiles with respect to parameters

underlying peak (Cmax) and overall drug exposure (AUC) in subjects with

normal

and impaired hepatic function. However, plasma exposure of LdT is renal

function dependent.

Subjects with mild, moderate and severe renal impairment treated with a

single

dose of 600, 400 and 200 mg LdT, respectively, had comparable overall plasma

exposure to normal subjects treated with 600 mg LdT.

<graph>

Conclusion

LdT is well tolerated in all subjects. While no dose modification is

necessary

in patients with hepatic impairment, dose adjustment is recommended for

subjects with moderate or severe renal impairment by reducing LdT daily

dose.

Idenix Pharmaceuticals, Inc, Cambridge MA, USA.

04/21/04

Reference

XJ Zhou and others. CLINICAL PHARMACOKINETICS OF TELBIVUDINE, A POTENT

ANTIVIRAL FOR HEPATITIS B, IN SUBJECTS WITH IMPAIRED HEPATIC OR RENAL

FUNCTION. Abstract 452. 39th EASL. April 14-18, 2004. Berlin, Germany.

[Guest guest]

Clinical Pharmacokinetics of Telbivudine (LdT) in Patients with Impaired

Hepatic or Renal Function

Telbivudine (LdT) is a L-nucleoside with potent anti-HBV activity. This drug

is currently being studied in clinical trials in patients with chronic

hepatitis B, with compensated and decompensated liver function. LdT is

predominantly eliminated via renal clearance as unchanged drug with minimal

hepatic elimination.

The hepatic impairment study enrolled 24 subjects with normal (n=6) and

impaired hepatic function (child-Pugh Score 5-6, 7-9 and 10-15,

n=6/category).

Subjects received a single dose of 600 mg LdT.

The renal impairment study enrolled 29 subjects with normal (creatinine

clearance (CLCR) > 80 ml/min, n=8) and impaired renal function (Mild: CLCR

50-80 ml/min, n=8; Moderate: 30-49 ml/min, n=7; Severe: < 29 ml/min, n=6).

Subjects received a reduced dose as renal function decreases.

Results

LdT exhibited comparable pharmacokinetic profiles with respect to parameters

underlying peak (Cmax) and overall drug exposure (AUC) in subjects with

normal

and impaired hepatic function. However, plasma exposure of LdT is renal

function dependent.

Subjects with mild, moderate and severe renal impairment treated with a

single

dose of 600, 400 and 200 mg LdT, respectively, had comparable overall plasma

exposure to normal subjects treated with 600 mg LdT.

<graph>

Conclusion

LdT is well tolerated in all subjects. While no dose modification is

necessary

in patients with hepatic impairment, dose adjustment is recommended for

subjects with moderate or severe renal impairment by reducing LdT daily

dose.

Idenix Pharmaceuticals, Inc, Cambridge MA, USA.

04/21/04

Reference

XJ Zhou and others. CLINICAL PHARMACOKINETICS OF TELBIVUDINE, A POTENT

ANTIVIRAL FOR HEPATITIS B, IN SUBJECTS WITH IMPAIRED HEPATIC OR RENAL

FUNCTION. Abstract 452. 39th EASL. April 14-18, 2004. Berlin, Germany.

[Guest guest]

Clinical Pharmacokinetics of Telbivudine (LdT) in Patients with Impaired

Hepatic or Renal Function

Telbivudine (LdT) is a L-nucleoside with potent anti-HBV activity. This drug

is currently being studied in clinical trials in patients with chronic

hepatitis B, with compensated and decompensated liver function. LdT is

predominantly eliminated via renal clearance as unchanged drug with minimal

hepatic elimination.

The hepatic impairment study enrolled 24 subjects with normal (n=6) and

impaired hepatic function (child-Pugh Score 5-6, 7-9 and 10-15,

n=6/category).

Subjects received a single dose of 600 mg LdT.

The renal impairment study enrolled 29 subjects with normal (creatinine

clearance (CLCR) > 80 ml/min, n=8) and impaired renal function (Mild: CLCR

50-80 ml/min, n=8; Moderate: 30-49 ml/min, n=7; Severe: < 29 ml/min, n=6).

Subjects received a reduced dose as renal function decreases.

Results

LdT exhibited comparable pharmacokinetic profiles with respect to parameters

underlying peak (Cmax) and overall drug exposure (AUC) in subjects with

normal

and impaired hepatic function. However, plasma exposure of LdT is renal

function dependent.

Subjects with mild, moderate and severe renal impairment treated with a

single

dose of 600, 400 and 200 mg LdT, respectively, had comparable overall plasma

exposure to normal subjects treated with 600 mg LdT.

<graph>

Conclusion

LdT is well tolerated in all subjects. While no dose modification is

necessary

in patients with hepatic impairment, dose adjustment is recommended for

subjects with moderate or severe renal impairment by reducing LdT daily

dose.

Idenix Pharmaceuticals, Inc, Cambridge MA, USA.

04/21/04

Reference

XJ Zhou and others. CLINICAL PHARMACOKINETICS OF TELBIVUDINE, A POTENT

ANTIVIRAL FOR HEPATITIS B, IN SUBJECTS WITH IMPAIRED HEPATIC OR RENAL

FUNCTION. Abstract 452. 39th EASL. April 14-18, 2004. Berlin, Germany.