Plasma Phenytoin Levels Research Articles

To Study Perioperative Changes in Plasma Phenytoin Levels in Patients with Brain Tumor Undergoing Craniotomy and Its Correlation with Postoperative Seizures

Abstract Introduction Phenytoin, although commonly used for postoperative seizure prophylaxis, exhibits variable results in mitigating seizure frequency following craniotomy. These discrepancies may be linked to a reduction in plasma phenytoin levels subsequent to the surgical intervention. Aims This prospective study aims to characterize changes in plasma phenytoin levels after craniotomy and their relationship with intraoperative blood loss. Methods Fifty consecutive patients were enrolled in this study after obtaining written informed consent. These patients had either been on oral phenytoin for at least 7 days or had received an intravenous loading dose before undergoing craniotomy. Serum phenytoin levels were measured 24 hours preoperatively, immediately before craniotomy (prior to skin incision), postcraniotomy (after skin closure), and 24 hours postcraniotomy. Additionally, intraoperative blood loss was calculated using a modified Gross formula. Results Immediately following craniotomy, there was a statistically significant mean decline of 28.16% in serum phenytoin levels. Furthermore, the analysis revealed a robust positive correlation between the decrease in phenytoin concentration level and several factors, including blood loss during surgery, the duration of the surgical procedure, intravenous fluids administered during surgery, and the occurrence of postoperative seizures. Conclusion This study underscores the potential utility of routinely measuring perioperative serum phenytoin levels in high-risk patients to prevent postcraniotomy seizures. Moreover, it suggests that patients with substantial intraoperative blood loss may benefit from an additional bolus dose of phenytoin toward the end of the surgical procedure.

Interaction of Phenytoin with Enteral Formulas, Proteins, and Dietary Fiber in Vitro and in Vivo

Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R® were co-administered, the time to maximum plasma concentration (Tmax) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC0-6 h) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ®. These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC0-6 h. These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.

No Detectable Phenytoin Plasma Levels After Topical Phenytoin Cream Application in Chronic Pain: Inferences for Mechanisms of Action.

PurposeTopical phenytoin can act as an analgesic in chronic pain, but it is unclear if topical phenytoin gives rise to systemic side effects. Therefore, the aim of this study is: 1) to evaluate safety in chronic pain patients who used topical phenytoin up to 30% applied daily on intact skin and mucous membrane, through determining phenytoin plasma levels; and 2) to elaborate on the analgesic mechanism of action.Patients and MethodsIn this retrospective study, we collected demographic and clinical data from 33 chronic pain patients who used 10% to 30% phenytoin cream, and in whom blood samples were drawn for phenytoin concentration measurement between January 2017 until September 2020. The instruction was to withdraw blood 1 to 4 hours after the last topical phenytoin application. The primary outcome was the detectability of plasma phenytoin after daily use of topical phenytoin.ResultsBlood withdrawal was carried out after on average 14 treatment days with topical phenytoin and on average 2.5 hours after topical phenytoin application. The median daily applied amount of phenytoin cream was 1.2 grams, resulting in a median daily amount of 120 mg phenytoin on the skin. Phenytoin levels were below the limit of detection in all patients and no side effects were reported.ConclusionPlasma phenytoin levels were below the limit of detection after topical use of phenytoin cream formulations up to 30% on intact skin and mucous membrane for the treatment of chronic pain, without side effects emerging. This finding suggests that the mechanism of analgesic action resides in the skin.

Interpretation of plasma levels of phenytoin and vaproate administraded enterally in hypoalbuminemic female patient

Interpretation of plasma levels of phenytoin and vaproate administraded enterally in hypoalbuminemic female patient

Iatrogenic phenytoin toxicity – Newer lessons learnt

Phenytoin is a widely prescribed anti-epileptic drug (AED), but overdoses are common given its narrow therapeutic index. A 24-year-old male, a previously diagnosed case of seizure disorder on multiple AEDs, including phenytoin presented with breakthrough seizures to the medical emergency. The subsequent medical management of this patient led to an inadvertent iatrogenic overdose of phenytoin resulting in encephalopathy in this patient. Given our experience in this patient, we suggest using a newer class of AED for seizure control in a patient already on phenytoin, particularly if immediate therapeutic plasma phenytoin level monitoring is not readily available.

Dosage of phenytoin in neurocritical patients using Bayesian algorithms: a pilot study

Phenytoin is widely used in neurocritical patients. Owing to its high pharmacokinetic variability and narrow therapeutic range, plasma level-guided dosing has become the standard. Bayesian prediction (BP) is considered the most flexible and precise pharmacokinetic strategy among several options. A retrospective study of BP dosage adjustment in 20 patients (35 plasma measures) was developed. Results indicated that 70% of phenytoin plasma levels of first plasma samples were beyond the therapeutic range. Phenytoin doses were also estimated according to BP for all patients. The measurements confirmed the ability of the strategy to lead to optimal dosage in 80% of patients, thus indicating a three-fold improvement over the basing dosage adjustment recommended in the literature.

Comparative bioavailability study of phenytoin in healthy Nepalese volunteers

Our study aimed to assess and compare the bioavailability of Eptoin 100 mg and Epileptin 100mg tablets in Nepalese healthy volunteers. A randomized, two-treatment cross-over study with two weeks’ wash-out period was conducted in 12 healthy non-smoker and non-alcoholic Nepalese male volunteers over a period of 6 months in the department of Clinical Pharmacology and Therapeutic at B. P. Koirala Institute of Health Sciences, Dharan, Nepal after approval from the Institutional Review Committee. The participants were randomized using sealed envelope system and received a single 100 mg oral tablet of either of the formulations with a two week washout period. Blood samples were collected predose and at regular intervals postdose upto 72 hours. Plasma phenytoin levels were estimated by reverse phase high performance liquid chromatography. The analytical method was validated prior to the start of study. Cmax (Peak Plasma Concentration), Tmax (Time to achieve maximum Plasma Concentration), AUC0-72 (Area under plasma concentration time curve 0 to 72 hours), AUC0-∞ (Area under plasma concentration time curve 0 to ∞) and T½ (Elimination half-life) and Kel (Elimination rate constant) were calculated and 80-120% margin (90% confidence interval) was used to assess bioequivalence. ANOVA test was used to analyze the data at P-value of 0.05. All volunteers completed the study. The log-transformed values of Cmax, Tmax, AUC0-t, and AUC0-∞ of the both formulations were within the specified limits and were bioequivalent according to the regulatory definition of bioequivalence based on the rate and extent of absorption. Both products can be considered equally effective in medical practice.
 Keywords: Bioavailability, Bioequivalence, healthy volunteer, Nepal, phenytoin sodium.

DRESS after IV phenytoin associated with cytochrome P450 CYP2C9*3 homozygosity

Phenytoin is a first-generation antiepileptic drug, which is used in the treatment of focal seizures and as standard of care for patients with benzodiazepine-refractory status epilepticus. Elimination of phenytoin occurs primarily via CYP enzyme–dependent hepatic clearance. The first step is the para-hydroxylation from active phenytoin to inactive hydroxy-phenytoin, which is dependent on CYP2C9 and, to a lesser extent, on CYP2C19. A considerable disparity in CYP2C9 alleles exists, and the frequency varies among different ancestry groups, the CYP2C9*3 allele being less frequent in Caucasians and more frequent in Asian populations.1,2 Homozygosity for the CYP2C9*3 allele leads to a significant reduction in enzyme activity, resulting in increased plasma levels of phenytoin.3

Phenytoin Cream for the Treatment for Neuropathic Pain: Case Series.

BACKGROUND: Neuropathic pain can be disabling, and is often difficult to treat. Within a year, over half of all patients stop taking their prescribed neuropathic pain medication, which is most probably due to side effects or disappointing analgesic results. Therefore, new therapies are needed to alleviate neuropathic pain. As such, topical analgesics could be a new inroad in the treatment of neuropathic pain. In 2014, we developed a new topical formulation containing either phenytoin or sodium phenytoin. After optimization of the formulation, we were able to reach a 10% concentration and combine phenytoin with other co-analgesics in the same base cream. OBJECTIVE: To describe a series of 70 neuropathic pain patients who were treated with phenytoin cream. MATERIAL AND METHODS: Cases treated with phenytoin 5% or 10% creams were gathered. The mean onset of pain relief, the duration of effect, and reduction in pain intensity measured on the 11-point numerical rating scale (NRS) were all studied. A single-blind response test with phenytoin 10% and placebo creams was conducted on 12 patients in order to select responders prior to prescribing the active cream. Plasma phenytoin concentrations were measured in 16 patients. RESULTS: Nine patients applied phenytoin 5% cream, and 61 patients used phenytoin 10% cream. After grouping the effects of all of the patients, the mean onset of pain relief was 16.3 min (SD: 14.8), the mean duration of analgesia was 8.1 h (SD: 9.1), and the mean pain reduction on the NRS was 61.2% (SD: 25.0). The mean pain reduction on the NRS while using phenytoin cream was statistically significant compared with the baseline, with a reduction of 4.5 (CI: 4.0 to 5.0, p < 0.01). The 12 patients on whom a single-blind response test was performed experienced a statistically significant reduction in pain in the area where the phenytoin 10% cream was applied in comparison to the area where the placebo cream was applied (p < 0.01). Thirty minutes after the test application, the mean pain reduction on the NRS in the areas where the phenytoin 10% cream and the placebo cream were applied was 3.3 (CI: 2.3 to 4.4, p < 0.01) and 1.1 (CI: 0.4 to 1.9, p < 0.05), respectively. In all 16 patients, the phenytoin plasma levels were below the limit of detection. So far, no systemic side effects were reported. Two patients only reported local side effects: a transient burning aggravation and skin rash. CONCLUSION: In this case series, the phenytoin cream had reduced neuropathic pain considerably, with a fast onset of analgesic effect.

Posttranslational Sodium ion Channel Modifications and the use of Topical Phenytoin in Painful Diabetic Neuropathy (PDN)

Phenytoin is a broad acting sodium channel blocker we deem fit for topical formulations to treat localized peripheral neuropathic pain. We tested this cream in a number of patients suffering from neuropathic pain syndromes and found it to be especially of use in small fiber neuropathic pain and in painful diabetic neuropathy. The fact that patients report an onset of action within 30 minutes, and the absence of detectable plasma levels of phenytoin, support an intra-epidermal mechanism of action. In this paper, we launch a hypothesis why phenytoin might be of particular use in peripheral neuropathic pain syndromes such as painful diabetic neuropathy

Topical Phenytoin Cream Reduces Burning Pain Due to Small Fiber Neuropathy in Sarcoidosis

We present a patient case of burning pain and sleep disturbances due to small fiber neuropathy (SFN) in sarcoidosis, treated successfully by topically applied phenytoin 10% cream. Using a single blind, placebo-controlled response test, the patient identified that within a 10 minute period phenytoin 10% cream provided a pain reduction of 50%, while placebo cream did not reduce pain at all. Subsequently, the patient was prescribed phenytoin 10% cream and used this cream for several weeks. Burning pain was reduced by 50% to 60%, resulting in a much improved sleep. The onset of analgesia starts around five minutes after the application of phenytoin 10% cream and in this case lasts for around 20 hours. Plasma levels of phenytoin, measured in 15 comparable patients were below the level of detection, ruling out systemic analgesia. Our hypothesis is that topical phenytoin influences epidermal targets such as nociceptors, small nerve fibers and keratinocytes, all which play a role in the pathogenesis of pain in SFN.

Phenytoin: neuroprotection or neurotoxicity?

Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin. We have reviewed the literature and concluded there is some supportive evidence for a reversible polyneuropathy after the oral use of phenytoin, though with no evidence for clear neurotoxicity on the level of peripheral nerves. This is probably due to the fact that the pharmacological effects of phenytoin, based on the stabilizing effect of the voltage-gated sodium channels, make impairment of nerve conduction in asymptomatic and symptomatic reversible polyneuropathies plausible. Clear toxically-induced phenytoin-related polyneuropathies, however, are extremely rare and are always related to high dose or high plasma levels of phenytoin, mostly developing during many years of therapy. We could only find one case of a probable reversible chronic phenytoin intoxication resulting in a biopsy proven axonal atrophy with secondary demyelination and signs of remyelination. All case series and case reports published are insufficient in detail to prove a clear causal relation between phenytoin intake and the induction of a peripheral polyneuropathy. Phenytoin does not lead to irreversible toxicity of the peripheral nerves and might, on the other hand, have neuroprotective properties.

Phenytoin: 80years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action.

In 1908 phenytoin (5,5-diphenylhydantoin) was first synthesized as a barbiturate derivative in Germany by professor Heinrich Biltz (1865-1943) and subsequently resynthesized by an American chemist of the pharmaceutical company Parke-Davis in 1923 in Detroit. Screening phenytoin did not reveal comparable sedative side effects as barbiturates and, thus, Parke-Davis discarded this compound as a useful drug. In 1936, phenytoin's anticonvulsive properties were identified via a new animal model for convulsive disorders, developed by Putnam and Merritt, who also evaluated its clinical value in a number of patients in the period 1937-1940. For many diseases, mechanism of action of phenytoin remains obscure. The voltage-gated sodium channel was and is generally regarded as the main target to explain phenytoin's activity as an anticonvulsant and an anti-arrhythmic drug. This target, however, does not explain many of the other clinical properties of phenytoin. We will explore a number of original articles on phenytoin published in its 80years history and give extra attention to the various hypothesis and experiments done to elucidate its mechanisms of action. Phenytoin has been explored in over 100 different disorders; the last two promising indications tested in the clinic are breast cancer and optic neuritis. Most probably, there are multiple targets active for these various disorders, and the insight into which targets are relevant is still very incomplete. It is remarkable that many pharmacological studies tested one dose only, mostly 50 or 100μM, doses which most probably are higher than the non-plasma bound phenytoin plasma levels obtained during treatment.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

Background & objectives:Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously.Methods:Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR.Results:The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group.Interpretation & conclusions:Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

Pharmacogenetics of ATP binding cassette transporter - MDR1 gene polymorphism (C3435T) and response to antiepileptic drug phenytoin pharmacokinetics in epilepsy

Background: Epilepsy is a common chronic neurological condition that is characterized by recurrent unprovoked seizures. A synonymous C to T variant at position 3435 (3435C N T) is one common polymorphism of the multidrug resistant 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein and form an important class of proteins for regulating pharmacokinetics. Phenytoin, a widely used anti-epileptic drug, exhibits marked inter-individual variation in Pharmacokinetics and attributed to genetic factors such as MDR1 polymorphism. Objective: The present study was undertaken to investigate the influence of MDR1 variant genotypes on Phenytoin Pharmacokinetics in the epileptic patients from Saudi Arabia. Material andmethods: 25 epileptic individuals with non-responders to phenytoin monotherapy and 25 epileptic subjects with responders to phenytoin monotherapy were recruited after getting their informed consent and genotyped for MDR1 (3435C N T) polymorphisms by Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Allele frequencies were derived from genotypic data Phenytoin plasma levels were analyzed by reverse phase HPLC method and Pharmacokinetic parameters were estimated by non-compartmental analysis using PK solutions software. Results: The MDR1 (3435C N T) polymorphism was seen to be in Hardy–Weinberg equilibrium and showed significant allelic association and genotypic association between non responders and responders to phenytoin (P b 0.01). The pharmacokinetics parameters in homozygous mutant group showed longer half-life (t1/ 2= 33.26 hrs) and less clearance rate (CL=0.42 L/hr) when compared to wild type group (t 1/2=19.2 hrs, CL=0.8 L/hr). Conclusion: Our finding suggest that the MDR1 genetic polymorphism influences Phenytoin Pharmacokinetics. So the therapeutic outcome of MDR1 (C3435T) genotype together with pharmacokinetic measurements might be useful in the context of improving the individualized efficacy of therapy in non-responders to phenytoin.

Combination of Capecitabine and Phenytoin May Cause Phenytoin Intoxication

Capecitabine is an oral antineoplastic agent, and phenytoin is an anticonvulsant drug with a narrow therapeutic index. Although the interaction between capecitabine and phenytoin is rare, it may be potentially fatal. This interaction is thought to be at the level of CYP2C9 isoenzyme system in the liver. Here, we present a patient with metastatic breast cancer who developed phenytoin intoxication when using capecitabine and phenytoin together. Closely monitoring plasma phenytoin levels is essential if capecitabine is used with phenytoin concurrently.

Evaluation of changes in serum phenytoin level after craniotomy and its relation to intra operative blood loss

Problems consideredPhenytoin is the drug of choice for post operative seizures while some studies have shown lack of efficacy of phenytoin in reducing seizure frequency after craniotomy, which in turn may be due to fall in plasma phenytoin levels after craniotomy. AimsThe aim of the study is to describe changes, if any, in plasma phenytoin levels after craniotomy and its relation to intra operative blood loss. MethodsThis was a prospective study in which total of 50 consecutive patients were enrolled after taking written informed consent, who were either on oral phenytoin for at least 7 days or had received intravenous loading dose prior to craniotomy. All patients had serum phenytoin levels monitored 24 h pre operatively, immediately pre craniotomy before skin incision and post craniotomy after skin closure, and 24 h after craniotomy. All patients had intra operative blood loss calculated with help of modification of Gross formula. ResultsThere was a mean fall of 23.6% in serum phenytoin level immediately following craniotomy which was statistically significant. Furthermore, analysis indicated that greater the operative duration and blood loss, greater was the fall in serum phenytoin level. ConclusionsThe study concludes that routine measurement of perioperative serum phenytoin levels in high risk patients may be of benefit in preventing post craniotomy seizures and an additional bolus dose should be given towards the end of surgery to patients with significant intra operative blood loss.

Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers

Objective:To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference.Materials and Methods:A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence.Results:Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits.Conclusion:Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group) saline (10 ml/kg) and phenytoin (30 mg/kg) were administered daily by intragastric gavage. In group 2 (test group) , pioglitazone (10 mg/kg) was administered daily 60 minutes before phenytoin (30 mg/kg). Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA), and phenytoin concentration in rat plasma was determined by High performance liquid chromatography (HPLC).The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03 µg/ml VS 1.2 ± 0.02 µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures.

PP139—Association of ABCB1, ABCC2, CYP2C9 and CYP2C19 polymorphism with phenytoin plasma concentrations

Epilepsy is the most prevalent chronic neurologic disorder that affects 65 million people worldwide. Phenytoin (PHT) is 1 of the most widely prescribed antiepileptic drugs (AEDs); however, large interindividual variability in doses and concentrations has been observed in epilepsy treatment with PHT. Functional polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and drug targets have been suggested to contribute to this genetic variability. To evaluate the association of CYP2C9, CYP2C19, ABCB1, and ABCC2 polymorphism on PHT plasma levels in epileptic patients. The present investigation was carried out in 57 consecutive patients (16–65 years) suffering epilepsy and treated with phenytoin. Approval from the institutional biomedical research ethics committee and the informed consent of patients was obtained before enrollment into the study. Genomic DNA was isolated from blood samples by standard technique. Genotyping of CYP2C9*2, CYP2C19*2 and *3, ABCB1 C1234T, C3435T, G2677A/T, ABCC2 G24A, and G1249A was performed by real-time PCR using allele-specific probes, and CYP2C9*3 by PCR-RFLP. PHT plasma levels were determined by radioimmunoassay. Twenty-six patients showed PHT therapeutic levels (10–20 µg/mL), 24 subtherapeutic and 7 supratherapeutic. Three cases, 2 CYP2C9 *1/*2, and 1 CYP2C19*1/3, had subtherapeutic levels. Patients with wild-type ABCB1 and ABCC2 genotypes exhibited a tendency to have increased PHT plasma levels than patients with mutant genotypes. PHT plasma levels showed great variability among patients that was not statistically significant correlated to the genetic polymorphisms analyzed, although ABCB1 and ABCC2 wild-type genotypes showed a trend toward higher levels. Further investigations are needed with other candidate genes and a larger sample.