Population Pharmacokinetics of Phenytoin in Saudi Patients

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Population Pharmacokinetics of Phenytoin in
Saudi Patients
Thamer M. Al-Shammary M.S candidate
Supervised by
Hisham S. Abou-Auda, Ph.D.
Tawfeeq A. Al-Najjar, Ph.D.
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Contents

• Introduction
• Objectives
• Methodology
• Results and discussion
• Conclusion

3
Introduction
4
Introduction
Pharmacokinetics
5
Introduction
Pharmacokinetics
6
Introduction
Therapeutic uses
Generalized Tonic-Clonic (Grand mal) Simple and
Complex Partial seizures. Prevention of seizures
following trauma and neurosurgery. Status
epilepticus. Ventricualr Arrhythmia.
7
Introduction
Dosage
Children
Adults

• Loading dose
• 15-20 mg/kg/day (in 3 divided doses)
• Maintenance dose ( mg/kg/day)
• 6 m-3 yr 8 - 10
• 4-6 yr 7.5- 9
• 7-9 yr 7 - 8
• 10-16 yr 6 - 7

• Loading dose
• 15-20 mg/kg/day (in 3 divided doses)
• Maintenance dose
• 300 mg/day (or 5-6 mg/kg/day, as tid)

8
Introduction
Precautions and contraindications
Hypersensitivity to phenytoin Severe liver
disease Heart block, sinus bradycardia Pregnancy
(category D) and lactation Use with caution in
DM Elderly Pts with porphyria
9
Introduction
Drug interactions
?
or?
? PHT level
? PHT level
PHT level
CBZ Phenobarbital Rifampin Ethanol ( Alcohol )
Valproic acid Sodium valproate TCA,s
ethosuximidE INH Fluconazole Diazepam Estrogen
10
Introduction
Population Pharmacokinetics
Random Effects
Fixed effects
Underlying disease
Age Weight Sex
Intra- individual variability
Inter- individual variability
11
Introduction
Importance of Phenytoin monitoring
12
Introduction
Mcg/ml
Death
100
Status epilepticus and mental changes
40
45o lateral gaze nystagmus and ataxia
Serum phenytoin level
30
Far lateral nystagmus
20
Therapeutic range
10
Sub-therapeutic range
0
13
Introduction
South African
?mol/L
13.6

Vmax

6.5 mg/kg/day
37 pts 21 male 16 female
Prospective study For 1 year
14
Introduction
Japan
Km 3.67 mg/L
Vmax 369 mg/day
Retrospective study
220 pts 120 male 100 female

15
Introduction
Chinese
16
Objectives
17
Methodology
18
Methodology
Medical Records
Coding
Medical Records
Coding
Data collection ( KKUH )
Data Collection form
Lab
Lab
Analysis
19
Methodology
Inclusion and Exclusion criteria
Inclusion
Exclusion
Saudi Pts
Receive PHT 2 wks
Non-Saudi Pts
Receive PHT 2 wks
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Methodology
Data Analysis
NCSS
NONMEM
WinNonMix
SAAM
SPSS
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Results and Discussion
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Results and discussion
101Patients
58 Males (57.4)
43 Females (42.6)
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Japan
S.A
Vm 6.5 mg/kg/ day
Km 13.6 ?mol/l
Km 3.67 mg/L
Vm 369 mg/day
Saudi
Vm
Km
Chinese