MDR1 gene polymorphism and phenytoin pharmacokinetics in epilepsy

Background: Pharmacokinetics is a widely used anti-epileptic drug phenytoin, which exhibits noticeable inter-individual variations in efficacy. Genetic factors, such as MDR1 gene polymorphism may play a crucial role in drug response

Objective: To investigate the influence of MDR1 variant genotypes on Phenytoin Pharmacokinetics in epileptic patients

Design: A Case-Control Genetic Study

Setting: College of Medicine and Pharmacy, King Khalid University, Abha, Saudi Arabia

Method: Twenty-five epileptic patients non-responders to phenytoin monotherapy and 25 epileptic patients' responders to phenytoin monotherapy were recruited. DNA was isolated by conventional phenol-chloroform method. MDR1 [3435C>T] gene polymorphism was assessed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphisms [PCR-RFLP] method. Allelic and genotypic frequency were calculated. Reversed-phase High-Performance Liquid Chromatography [HPLC] method was used to determine the plasma levels of Phenytoin drug. PK Solutions was used for non-compartmental analysis to estimate the pharmacokinetic parameters

Result: The MDR1 [3435C>T] polymorphism was found to be in Hardy-Weinberg equilibrium and displayed significant allelic and genotypic association between non-responders and responders to phenytoin [P<0.01]. The finding of pharmacokinetics analysis demonstrated that longer halflife [t1/2 = 33.26 hours] and less clearance rate [CL = 0.42 L/hour] in the homozygous variant group compared to wild-type genotype group [t 1/2 = 19.2hrs, CL = 0.8 L/hour]

Conclusion: The finding suggests that the genetic polymorphism in the C3435T location of MDR1 gene might determine pharmacokinetics variability of phenytoin drug. Therefore, pharmacokinetics parameters along with genotyping of MDR1 [C3435T] genotype might be valuable in the perspective of personalized medicine in epileptic patients

Antihypertensive effect of methanolic extract of Passiflora nepalensis

The present study was designed to investigate the antihypertensive effect of methanolic extract of the whole plant of Passiflora nepalensis Walp., Passifloraceae, (MPN) in renal hypertensive and normotensive rats. The blood pressure, pulse pressure, and heart rate fell dose-dependently in renal hypertensive and normotensive rats after intravenous administration of 75, 150, and 225 mg/kg MPN, suggesting that MPN possesses antihypertensive, hypotensive and negative chronotropic effects. The effect at doses of 150 and 225 mg/kg of MPN were more pronounced than that of 75 mg/kg body weight. Thus, the present study reveals that MPN exerts antihypertensive effect against renal hypertension.