orodispersible tablet is bioequivalent to olanzapine coated tablets,
with a similar rate and extent of absorption. Olanzapine
orodispersible tablets may be used as an alternative to olanzapine
is well absorbed after oral administration, reaching peak plasma
concentrations within 5 to 8 hours. The absorption is not affected by
food. Absolute oral bioavailability relative to intravenous
administration has not been determined.
plasma protein binding of olanzapine was about 93% over the
concentration range of about 7 to about 1000 ng/ml. Olanzapine is
bound predominantly to albumin and α1-acid-glycoprotein.
is metabolised in the liver by conjugative and oxidative pathways.
The major circulating metabolite is the 10-N-glucuronide, which does
not pass the blood brain barrier. Cytochromes P450-CYP1A2 and
P450-CYP2D6 contribute to the formation of the N-desmethyl and
2-hydroxymethyl metabolites; both exhibited significantly less in
activity than olanzapine in animal studies. The predominant
pharmacologic activity is from the parent, olanzapine.
oral administration, the mean terminal elimination half-life of
olanzapine in healthy subjects varied on the basis of age and gender.
healthy elderly (65 and over) versus non-elderly subjects, the mean
elimination half-life was prolonged (51.8 versus 33.8 hours) and the
clearance was reduced (17.5 versus 18.2 l/hr). The pharmacokinetic
variability observed in the elderly is within the range for the
non-elderly. In 44 patients with schizophrenia >65 years of age,
dosing from 5 to 20 mg/day was not associated with any distinguishing
profile of adverse
female versus male subjects, the mean elimination half-life was
somewhat prolonged (36.7 versus 32.3 hours) and the clearance was
reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg)
demonstrated a comparable safety profile in female (n = 467) as in
male patients (n =
renally impaired patients (creatinine clearance <10ml/min) versus
healthy subjects, there was no significant difference in mean
elimination half-life (37.7 versus 32.4 hours) or clearance (21.2
versus 25.0 l/hr). A mass balance study showed that approximately 57%
of radiolabelled olanzapine appeared in urine, principally as
A small study of the effect of
impaired liver function in 6 subjects with clinically significant
(Childs Pugh Classification A (n = 5) and B (n = 1)) cirrhosis
revealed little effect on the pharmacokinetics of orally administered
olanzapine (2.5 – 7.5 mg single dose): Subjects with mild to
moderate hepatic dysfunction had slightly increased systemic
clearance and faster elimination half-time compared to subjects with
no hepatic dysfunction (n = 3). There were more smokers among
subjects with cirrhosis (4/6; 67 %) than among subjects with no
hepatic dysfunction (0/3; 0 %).
In smoking subjects with mild
hepatic dysfunction, mean elimination half-life (39.3 hours) was
prolonged and clearance (18.0 l/hr) was reduced analogous to
non-smoking healthy subjects (48.8 hours and 14.1 l/hr,
non-smoking versus smoking subjects (males and females), the mean
elimination half-life was prolonged (38.6 versus 30.4 hours) and the
clearance was reduced (18.6 versus 27.7 l/hr).
plasma clearance of olanzapine is lower in elderly versus young
subjects, in females versus males, and in non-smokers versus smokers.
However, the magnitude of the impact of age, gender, or smoking on
olanzapine clearance and half-life is small in comparison to the
overall variability between individuals.
a study of Caucasians, Japanese, and Chinese subjects, there were no
differences in the pharmacokinetic parameters among the three
(ages 13 to 17 years): The pharmacokinetics of olanzapine are similar
between adolescents and adults. In clinical studies, the average
olanzapine exposure was approximately 27% higher in adolescents.
Demographic differences between the adolescents and adults include a
lower average body weight and fewer adolescents were smokers. Such
factors possibly contribute to the higher average exposure observed
[Summary of Product Characteristics]. Utrecht, The Netherlands: Eli
Lilly Nederland B.V.