Absorption
Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours.
Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.
Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 μg/ml and 20 μg/ml in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.
Table 3
Summary of gabapentin mean (%CV) steady-state pharmacokinetic parameters
following every eight hours administration
|
Pharmacokinetic parameter |
300 mg
(N=7) |
400 mg
(N=14) |
800 mg
(N=14) |
|
Cmax (µg/ml)
tmax (hr)
T1/2(hr)
AUC (0-8)
µg•hr/ml)
Ae%(%) |
Mean
4.02
2.7
5.2
24.8
NA |
%CV
(24)
(18)
(12)
(24)
NA |
Mean
5.74
2.1
10.8
34.5
47.2 |
%CV
(38)
(54)
(89)
(34)
(25) |
Mean
8.71
1.6
10.6
51.4
34.4 |
%CV
(29)
(76)
(41)
(27)
(37) |
|
|
|
|
|
|
|
Cmax = Maximum steady state plasma concentration
tmax = Time for Cmax
T1/2 = Elimination half-life
AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours postdose
Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose
NA = Not available
Distribution
Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.
Biotransformation
There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
Elimination
Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.
In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.
Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see section 4.2).
Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.
In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.
Linearity/Non-linearity
Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.
Absorption
Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours.
Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.
Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 μg/ml and 20 μg/ml in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.
Table 3
Summary of gabapentin mean (%CV) steady-state pharmacokinetic parameters
following every eight hours administration
|
Pharmacokinetic parameter |
300 mg
(N=7) |
400 mg
(N=14) |
800 mg
(N=14) |
|
Cmax (µg/ml)
tmax (hr)
T1/2(hr)
AUC (0-8)
µg•hr/ml)
Ae%(%) |
Mean
4.02
2.7
5.2
24.8
NA |
%CV
(24)
(18)
(12)
(24)
NA |
Mean
5.74
2.1
10.8
34.5
47.2 |
%CV
(38)
(54)
(89)
(34)
(25) |
Mean
8.71
1.6
10.6
51.4
34.4 |
%CV
(29)
(76)
(41)
(27)
(37) |
Cmax = Maximum steady state plasma concentration
tmax = Time for Cmax
T1/2 = Elimination half-life
AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours postdose
Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose
NA = Not available
Distribution
Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.
Biotransformation
There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
Elimination
Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.
In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.
Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see section 4.2).
Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.
In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.
Linearity/Non-linearity
Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.