Search

Background and Objectives: A high inter-individual variability in the pharmacokinetics of lamotrigine has been observed. Lamotrigine is primarily metabolized by UGT1A4 and UGT2B7, both of which show genetic polymorphisms. Both genetic and non-genetic factors may influence the pharmacokinetics of lamotrigine. The aim of this study was to determine the pharmacokinetic parameters of lamotrigine and to investigate the effect of genetic variants of UGT1A4 and UGT2B7 and various non-genetic factors on its pharmacokinetics., Methods: Four single nucleotide polymorphisms (SNPs; UGT1A4 142 T>G, UGT1A4 70C>T, UGT2B7 372A>G, UGT2B7 -161C>T) were identified using the TaqMan Allelic Discrimination Assay. Data were analyzed using NONMEM. Model evaluation was performed using the bootstrap approach and predictive check., Results: A total of 116 samples were obtained from 75 patients and included in the population analysis. The use of enzyme inducers, valproic acid, and the UGT2B7-161 C>T SNP were found to significantly influence lamotrigine apparent clearance (CL/F). Lamotrigine CL/F in patients carrying the UGT2B7 -161 CT or TT SNP was 18% lower than that in patients carrying the UGT2B7 -161 CC SNP., Conclusion: Both genetic and non-genetic factors were found to influence lamotrigine pharmacokinetics. These factors should be considered when determining lamotrigine dosing. The model presented here could be useful for lamotrigine dose adjustment in clinical practice.

Purpose: To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA)., Methods: Retrospective data were collected from an electronic database and medical records. Blood samples were obtained and drug concentrations analyzed as a part of routine therapeutic drug monitoring (TDM). Screening for wild-type CYP3A5*1 and CYP3A5*3 single nucleotide polymorphism (rs776746) by allelic discrimination assay using real-time polymerase chain reaction technique (real-time PCR) was performed. Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared., Results: Of the 70 patients assessed, 8 (11%) patients were homozygous CYP3A5*1/*1, 28 (40%) patients were heterozygous CYP3A5*1/*3, and 34 (49%) patients were homozygous CYP3A5*3/*3. The CBZ clearance and dose-adjusted CBZ levels did not significantly differ between patients with CYP3A5*1 and CYP3A5*3 alleles when CBZ was used as monotherapy. For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded. Nevertheless, it was observed that AEDs significantly increased CBZ clearance only in patients carrying the active CYP3A5*1 allele., Conclusions: When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers. The dosage regimen should be adjusted accordingly to gain a better clinical outcome.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Background: Since its first clinical use more than 30 years ago, Valproic acid is still being widely prescribed It has been available in Thailand for more than 20 years. Sodium valproate slow-released (SVSR) form has been used in clinical practice in Thailand since 1990. The objectives of this open study were to access the compliance and satisfaction consequences in the epileptic patients., Material and Method: In this prospective, multi-center study, the authors compared the compliance and satisfaction consequences in epileptic patients switched from more than two times daily sodium valproate enteric-coated tablet (SVEC) regimen to the same total daily dose of SVSR form given once or twice daily., Results: Eighty-nine of the 100 patients completed the study. 43.8% were male (39 of 89 patients). Mean age was 34.74 +/- 12.67 years. Most common etiology of epilepsy was idiopathic 40.4%. Patients were very/fairly happy with the SVSR form 94.4% compared to the SVEC form 56.2% (p = 0.000). Patients had been experiencing no problem with the SVSR form 67.4% compared to SVEC form 38.2% (p = 0.000) and also never missing taking SVSR. form 77.5% compared to SVEC form 40.4% (p = 0.000). According to convenience, patients preferred to administer SVSR form once a day 92.1% and never over taking dosed the antiepileptic drug 96.6%. SVSR form had fewer side effects than the enteric-coated form interms of memory problem (40.4% vs 48.3%) (p = 0.000), sleepiness (30.3% vs 42.7%) (p = 0.041) and difficulty in thinking clearly (38.2% vs 44.9%) (p = 0.001). The patients were seizure free during the study period comparing SVSR form 76.4% to SVEC form 65.2% (p = 0.011)., Conclusion: Patients preferred once daily regime. Switching from SVEC to SVSR form increased seizure free, reduced side effects, improved patient's compliance and satisfaction.

Background: Epilepsy is a common disease but to achieve successful seizure control in developing countries is still a challenge. This study aimed to investigate the epilepsy services in Thailand. Methods: This was a survey by questionnaires on epilepsy service sent to 1,033 public hospitals all over Thailand. Results: The response rate was 54.1%. The results show that most of physicians that provide care for persons with epilepsy were General Practitioners (91.5%). Epileptologists and Neurologists accounted for only 11.1% and 14.4%. There were only 52 EEG, 54 CT Scan, and 6 MRI instruments in the entire country of 65 million. Standard antiepileptic drugs (AEDs) were widely available, phenobarbital (99.9%), phenytoin (96.0%), carbamazepine (97.9%), and valproic acid (89%) of institutions. The availability of new AEDs were: gabapentin (77.6%), topiramate (63.9%), levetiracetam (46.0%), lamotrigine (45.3%), pregabalin (33.6%), were also available in 77.6%, 63.9%, 46.0%, 45.3%, 33.6%, vigabatrin (14.5%), and oxcarbazepine (14.3%) of institutions. Intravenous AEDs used for status epilepticus patients include phenytoin (54.2%), phenobarbital (33.9%), and sodium valproate (12.1%). Therapeutic drug monitoring could be done in 45.7% of the responding hospitals. Conclusion: There is limited human and material resources for the care of epilepsy in Thailand. There is a need to develop a model of epilepsy care that is appropriate with the limited resources in the country. [ABSTRACT FROM AUTHOR]

Abstract: Background: When phenytoin is prescribed for administration via nasogastric tube, immediate-release OR) phenytoin tablets are crushed before use and extended-release (ER) phenytoin capsules are opened and only the granules are used. However, it is unknown whether the same dose of these 2 different formulations will result in the same steady-state serum phenytoin concentration. Objective: The aim of this study was to determine whether ER phenytoin capsules can be used interchangeably with IR phenytoin tablets for prophylaxis of posttraumatic seizures. Methods: Inpatients at the neurosurgical ward at Prasat Neurological Institute, Bangkok, Thailand, between October 2004 and October 2005 were enrolled in the study. All patients were initially prescribed IR phenytoin tablets 300 mg/d as a maintenance dose for prophylaxis of posttraumatic seizures. The serum phenytoin concentration was measured after ≥5 days of treatment with IR phenytoin tablets 300 mg/d (two 50-mg tablets every 8 hours) that had been crushed before being administered concomitantly with a blenderized diet through the nasogastric tube. Without a washout period, the dosage form was changed to ER phenytoin capsules (three 100-mg capsules QD). The capsules were opened and the contents were administered concomitantly with the blenderized diet through the nasogastric tube for ≥5 days. The serum phenytoin concentration was again determined. The patients were closely monitored for seizures and adverse events (AEs). Results: Thirty-three patients enrolled in the study and 17 (10 women, 7 men; mean [SD] age, 62.94 [15.94] years [range, 18-89 years]) completed the study. The mean (SD) serum phenytoin concentrations after administration of phenytoin tablets and capsules were 6.03 (5.92) μg/mL and 3.80 (2.71) μg/mL, respectively (P = 0.019). The mean serum phenytoin concentrations, adjusted for low serum albumin concentrations after administration of tablets and capsules, were calculated and reported to be 10.33 (11.60) μg/mL and 6.28 (4.76) μg/mL, respectively (P = 0.035). The maximum phenytoin metabolic rate (Vmax) (assuming the substrate concentration at which the rate of metabolism is one half Vmax = 4 mg/L) after the administration of phenytoin tablets and capsules was 8.37 (2.42) mg/kg · d-1 and 10.38 (6.48) mg/kg · d-1, respectively. These values were not significantly different. All patients were seizure-free and no AEs were observed. Conclusion: The steady-state serum phenytoin concentration was significantly lower with ER phenytoin capsules 300 mg/d than IR phenytoin tablets 300 mg/d administered via nasogastric feeding tube concomitantly administered with a blenderized diet in these neurosurgical patients. Key words: phenytoin nasogastric tube feeding extended-release capsule immediate-release tablet [Copyright &y& Elsevier]