e timolol group. The non-PCG (e.g. juvenile open angle glaucoma, aphakic glaucoma) subgroup showed similar results as the PCG subgroup.
The effect on IOP was seen after the first week of treatment (see table) and was maintained throughout the 12 week period of stud
|
Table: IOP reduction (mmHg) at week 12 by active treatment group and baseline diagnosis
|
|
|
Latanoprost
N=53
|
Timolol
N=54
|
|
Baseline Mean (SE)
|
27.3 (0.75)
|
27.8 (0.84)
|
|
Week 12 Change from Baseline Mean†(SE)
|
-7.18 (0.81)
|
-5.72 (0.81)
|
|
p-value vs. timolol
|
0.2056
|
|
|
PCG
N=28
|
Non-PCG
N=25
|
PCG
N=26
|
Non-PCG
N=28
|
|
Baseline Mean (SE)
|
26.5 (0.72)
|
28.2 (1.37)
|
26.3 (0.95)
|
29.1 (1.33)
|
|
Week 12 Change from Baseline Mean†(SE)
|
-5.90 (0.98)
|
-8.66 (1.25)
|
-5.34 (1.02)
|
-6.02 (1.18)
|
|
p-value vs. timolol
|
0.6957
|
0.1317
|
y, as in adults.
SE: standard error.
†Adjusted estimate based on an analysis of covariance (ANCOVA) model.
5.2 Pharmacokinetic properties
Latanoprost (mw 432.58) is an isopropyl ester prodrug which per se is inactive, but after hydrolysis to the acid of latanoprost becomes biologically active.
The prodrug is well absorbed through the cornea and all drug that enters the aqueous humour is hydrolysed during the passage through the cornea.
Studies in man indicate that the peak concentration in the aqueous humour is reached about two hours after topical administration. After topical application in monkeys, latanoprost is distributed primarily in the anterior segment, the conjunctivae and the eyelids. Only minute quantities of the drug reach the posterior segment.
There is practically no metabolism of the acid of latanoprost in the eye. The main metabolism occurs in the liver. The half life in plasma is 17 minutes in man. The main metabolites, the 1,2-dinor and 1,2,3,4-tetranor metabolites, exert no or only weak biological activity in animal studies and are excreted primarily in the urine
Paediatric population
An open-label pharmacokinetic study of plasma latanoprost acid concentrations was undertaken in 22 adults and 25 paediatric patients (from birth to < 18 years of age) with ocular hypertension and glaucoma. All age groups were treated with latanoprost 0.005%, one drop daily in each eye for a minimum of 2 weeks. Latanoprost acid systemic exposure was approximately 2-fold higher in 3 to < 12 year olds and 6-fold higher in children < 3 years old compared with adults, but a wide sa
