Diazepam

1
Diazepam
2
Drug-Drug Interaction Studies Phenytoin

Drug
Oral
Change
Change
Change in
Study

dose

omeprazole
in CL

in AUC
C


ss
Population ()

(mg)

dose (mg)

()

()

()

Healthy subjects

250 (iv)

40 x 7
-
15

-

-

(n8)

days

Healthy subjects

300

40 x 7
-

19

-

(n10)

days

Healthy subjects

4.5
/kg

40 x 3
-

NC

-

(n18)

days

Epileptic patients

ss

20 x 21
-

-

NC

(n8)

days


3
Individual and Mean Plasma Concentrations
(?mol/L) of Phenytoin
4
Drug-Drug Interaction Studies Warfarin


Drug
Oral
Change
Change
Change

Study

dose

omeprazole
in CL

in AUC
in C


ss
Drug

Population ()

(mg)

dose (mg)

()

()

()

Warfarin
-

R

Healthy
4.7

20 x 14
-

-

12

Warfarin
-

S

subjects

days

NC

(n21)

Warfarin
-

R

Anticoag.
ss

20 x 21
-

-

9.5

Warfarin
-

S

Patients

days

NC

(n
28)


5
Variability in Coagulation with Warfarin
15
10
5
Delta Week 1 - Week 2
0
-5
-10
-15
0
5
10
15
20
25
TT Values at Week 1
6
Interaction Between Omeprazole and Warfarin in
Anticoagulant Patients
7
Summary Table Drug-Drug Interaction Studies
(contd)Effect of Omeprazole on the
Pharmacokinetics of Other Drugs
8
No Food Effect on the MUPS Tablet
9
Food Effect on MUPS
Parameter
FedMUPS Tablet
FastingMUPS Tablet
Fed/Fasting

• AUC (?mol x h/L) 0.81 (0.64-1.01) 0.81
  (0.65-1.02) 1.00 (0.84-1.18)
• Cmax (?mol/L) 0.38 (0.29-0.49) 0.57
  (0.43-0.74) 0.66 (0.51-0.86)
• tmax (h) 3.6 (1.0) 2.0 (1.0) --

AUC area under the plasma concentration versus
time curve Cmax maximum observed plasma
concentration tmax time of observed Cmax MUPS
multiple unit pellet system Geometric mean
(95 confidence interval) Arithmetic mean
(standard deviation) h hours Data from study
SH-OME-008
10
(No Transcript)
11
Controlled Study of Intermittent Regimen
Treatment with Omeprazole

• Prognostic Factors for success with intermittent
  regimen treatment
• Symptoms controlled at 2-weeks is a powerful
  prognostic factor (plt0.0001)
• 33 of patients who responded to 2-weeks of
  therapy required no further treatment
• Other factors had no significant effect
• Grade of esophagitis at entry (p0.59)
• Duration of reflux symptoms (p0.39)
• Body mass index (p0.26)
• Presence of H. pylori (p0.63)
• Gender (p0.48)
• Age (p0.54)
• Bardhan et al., BMJ, 1999