Therapeutic monitoring of digoxin and antiepileptic drugs in Egypt and Saudi Arabia

Retrospective analysis was undertaken of serum drug levels determined in 1996 of 580 Egyptian and 1299 Saudi samples and in 2001 of 2361 Saudi samples. Monitored drugs were digoxin, carbamazepine, phenytoin, and valproic acid. The therapeutic drug monitoring results in 1996 showed no differences between the two countries in the rates of subtherapeutic, therapeutic, or toxic drug levels. When the levels of all drugs relative to therapeutic ranges were compared between the 1996 and 2001 Saudi data, a significant decrease in the rate of potentially toxic levels was seen in 2001.     

Visceral leishmaniasis in North West Saudi Arabia: a new endemic focus of L. donovani or further evidence of a changing pathogenic role for L. tropica?

OBJECTIVES: The objective of this study was to evaluate patients with VL from the city of Tabuk, Kingdom of Saudi Arabia, with particular reference to the possibility that a focus of VL exists in the North West Province of Saudi Arabia, an area where it had not previously been reported. SETTING: North West Armed Forces Hospital, Tabuk, Saudi Arabia. DESIGN: Retrospective evaluation of all cases of infantile visceral leishmaniasis diagnosed in Tabuk, Saudi Arabia between 1989 and 1994. RESULTS: 5 cases of infantile visceral leishmaniasis were reviewed. In four cases, no evidence of travel outside Tabuk could be identified, suggesting primary infection by viscerotropic Leishmanial organisms in this area of Saudi Arabia. CONCLUSIONS: Visceral leishmaniasis has been identified in an area previously not considered endemic for L. donovani. This observation may indicate either, a previously unrecognized focus of L. donovani or provide further evidence of a changing pathogenic role for L. tropica.     

Therapeutic monitoring of antiepileptic drugs: a comparison between a Czech and a Swedish University Hospital

Plasma concentrations obtained during routine therapeutic monitoring of antiepileptic drugs (AED) (N03A ATC group) were compared in patients treated with one or several AED in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of mean plasma concentrations (PC). The study included 2,824 adult out- and inpatients in Huddinge treated from 1995 to 1999 and 1,268 outpatients treated in Ostrava from 1993 to 2004. PC of valproic acid in Huddinge and all AED except clonazepam in Ostrava were analyzed with gas-liquid chromatography. Plasma concentrations of clonazepam in Ostrava and all AED except valproic acid in Huddinge were analyzed by HPLC. The differences in PC were tested by Student's t-test. Chi(2) method was used for the differences in the distribution of PC relative to the therapeutic window. The mean plasma concentrations generally reached the apparent therapeutic ranges but were below the range in the cases of phenytoin monotherapy in both hospitals, and clonazepam, phenobarbital and phenytoin in polytherapy in Ostrava. In monotherapy 33% of the analyses showed sub-therapeutic concentrations in Huddinge, compared to 38% in Ostrava. Eight percent of the analyses showed potentially toxic concentrations in Huddinge, but only 3% in Ostrava. The highest number of sub-therapeutic concentrations was detected for phenytoin in both hospitals: 59% in Huddinge, 78% in Ostrava. In polytherapy only slight differences between the hospitals were found. PC/dose ratios were significantly lower in polytherapy than in monotherapy for carbamazepine and valproic acid in both hospitals. In contrast a higher PC/dose ratio was found in polytherapy for phenytoin in both cohorts and for lamotrigine in Ostrava. Drug treatment of epilepsy in our two hospitals is surprisingly similar in terms of achieved plasma concentrations, in spite of socioeconomic and cultural differences between our two countries. This may be explained by the long experience with TDM in both hospitals, which has the inherent capacity to promote evidence based drug therapy.     

老年癫痫患者卡马西平、丙戊酸血药浓度监测结果分析

目的 探讨老年癫痫患者卡马西平、丙戊酸血药浓度监测情况。方法 对262例常规服用卡马西平、丙戊酸钠老年癫痫患者进行血药浓度监测。结果 卡马西平组有13.75%低于有效血药浓度,5%高于有效血药浓度,81.25%达到有效血药浓度。而丙戊酸组有51.96%低于有效血药浓度,3.92%高于有效血药浓度,44.12%达到有效血药浓度。丙戊酸组达到有效血药浓度的比率明显低于卡马西平组(P＜0.01),而两组高于有效血药浓度的比率基本相似(P＞0.05)。结论 患者在给予卡马西平或丙戊酸钠初次使用剂量后达到有效浓度的比率存在一定差异。临床医师在应用抗癫痫药物时应实施个体化给药。     

Inhibitory effect of valproic acid on the disposition of carbamazepine and carbamazepine-10,11-epoxide in the rat

The effects of valproic acid on the disposition of carbamazepine and carbamazepine epoxide were studied in conscious rats. Each animal received a constant rate infusion of carbamazepine and an iv bolus dose of epoxide in the presence and absence of valproate. The latter was maintained within its therapeutic range by iv infusion. Carbamazepine steady state clearance was decreased by 20.2 +/- 12.7% in the presence of valproate. The formation clearance of carbamazepine epoxide, which accounts for 50% of the total clearance, was decreased on the average by 22.7%. Also, a significant increase in the level of carbamazepine epoxide formed from carbamazepine was found in the presence of valproate. This increase in metabolite level was explained by the large reduction in epoxide clearance (41.6 +/- 13.1%) observed after single doses of epoxide. Based on this finding, a separate study examined the effect of valproate on the non-renal component of the clearance of carbamazepine epoxide. The non-renal clearance of epoxide was decreased by 59.9 +/- 11.9% in the presence of valproic acid.     

Combination therapy with carbamazepine and valproic acid in problem cases at an outpatient epilepsy clinic

A total of 64 problem patients with epilepsy (42 retrospective evaluations, 22 prospective cases) was treated with the combination of carbamazepine and valproic acid. Most frequent seizure types were tonic clonic (focal origin or primarily generalized), complex partial ones, and absences. Best results were observed in patients with tonic clonic seizures in contrast to complex partial ones. The pattern of adverse reactions (none of significant severity) was according to those of monotherapies with the compounds. In cases with relevant improvement serum levels of carbamazepine and valproic acid were within the range commonly described for monotherapies.     

Valproic acid toxicity: overview and management

Acute valproic acid intoxication is an increasing problem, accounting for more than 5000 calls to the American Association of Poison Control Centers in 2000. The purpose of this paper is to review the pharmacology and toxicology of valproic acid toxicity. Unlike earlier antiepileptic agents, valproic acid appears to function neither through sodium channel inhibition nor through direct gamma-aminobutyric acid agonism, but through an indirect increase in regional brain gamma-aminobutyric acid levels. Manifestations of acute valproic acid toxicity are myriad, and reflect both exaggerated therapeutic effect and impaired intermediary metabolism. Central nervous system depression is the most common finding noted in overdose, and may progress to coma and respiratory depression. Cerebral edema has also been observed. Although hepatotoxicity is rare in the acute overdose setting, pancreatitis and hyperammonemia have been reported. Metabolic and hematologic derangements have also been described. Management of acute valproic acid ingestion requires supportive care and close attention to the airway. The use of controversial adjunctive therapies, including extracorporeal drug elimination and L-carnitine supplementation, will be discussed.     

Use of lithium, carbamazepine, and valproic acid in a state-operated psychiatric hospital.

OBJECTIVE: To examine the prescribing of mood stabilizers (lithium, carbamazepine, and valproic acid) in a 500-bed state-operated psychiatric hospital in New York. METHODS: All 129 inpatients receiving mood stabilizers were identified and their medical records reviewed using a standardized drug use evaluation form. Diagnosis, other indications, and prior experience with mood stabilizers were examined, as well as outcome and adverse effects. RESULTS: Approximately one-quarter of the inpatient population received a mood stabilizer. The frequency of carbamazepine use exceeded the use of lithium, with 72 patients receiving carbamazepine and only 62 receiving lithium. Twenty-eight patients received valproic acid. Indications found most frequently for carbamazepine use included assaultive or aggressive behavior (70% for those receiving carbamazepine as the only mood stabilizer). Of those patients with bipolar or schizoaffective disorder and receiving either lithium, carbamazepine, or valproic acid, 36% were prescribed carbamazepine (10% as a first-line agent) and 50% lithium (26% as a first-line agent). None of these indications for carbamazepine has been approved by the Food and Drug Administration. In general, positive outcomes were documented but without supporting objective measures. Significant adverse effects were documented in the medical record in one-quarter of the patients. CONCLUSIONS: There was widespread use of the three mood stabilizers examined, singly and in combination, for a variety of indications. Lithium and valproic acid remain more frequently prescribed for the treatment of bipolar and schizoaffective disorders. Monotherapy with carbamazepine or valproic acid results in statistically significantly fewer adverse effects than lithium or combination therapy (p values between p = 0.00038 and p = 0.006). Current clinical practice has endorsed the use of carbamazepine for aggressive or assaultive behavior, although there does not appear to be sufficient proof of effectiveness in the literature. Formal studies of carbamazepine's antiagressive effects should be conducted.     

Pharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats

The present study investigates the interaction of curcumin with four antiepileptic drugs (AEDs) in male Wistar rats. In the first protocol, seizures were induced using pentylenetetrazole (PTZ) and valproate was injected intraperitoneally (i.p.) in therapeutic and sub-therapeutic doses 30 min before PTZ administration. Curcumin was co-administered with sub-therapeutic dose of valproate 60 min before PTZ injection. In the second protocol, seizures were induced by maximal-electroshock. Phenytoin, phenobarbitone and carbamazepine were injected in their therapeutic and sub-therapeutic doses 120, 60 and 30 min, respectively, before seizure induction. Curcumin was administered along with sub-therapeutic doses of phenytoin, phenobarbitone and carbamazepine, 60 min before induction of seizures. Behavioral parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were assessed and the serum levels of the AEDs were estimated. The AEDs in their therapeutic doses produced complete protection against seizures. However, sub-therapeutic doses of these AEDs failed to completely protect against seizures. Co-administration of curcumin with sub-therapeutic dose of valproate significantly increased the latency to myoclonic jerks. The percentage protection against seizures with sub-therapeutic doses of valproate, phenytoin, phenobarbitone and carbamazepine was also enhanced by concomitant curcumin administration. Both PTZ and MES induced seizures caused significant impairment of cognitive functions. Co-administration of curcumin with these AEDs in their sub-therapeutic doses prevented the impairment of learning and memory due to seizures whereas no such improvement was observed in the groups administered the sub-therapeutic doses of the AEDs alone. Additionally, curcumin reversed the oxidative stress due to seizures. However, curcumin co-administration did not cause any significant alteration in the serum levels of the AEDs. The results thus suggest the potential of curcumin as an adjunct to these AEDs in epilepsy with the advantage of increasing the efficacy, reducing the dose and side effects of the AEDs.     

Differences between prescribed daily doses and defined daily doses of antiepileptics--therapeutic drug monitoring as a marker of the quality of the treatment

OBJECTIVE: Prescribed daily doses (PDDs) of antiepileptics (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospital in Ostrava, Czechia. Plasma levels were used as an indicator of the quality of treatment. METHOD: Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of PDDs and plasma levels. The study included 1,144 in-patients examined in the period 1993 - 2004. The differences in PDD were tested by Mann-Whitney-U-test. ATC/DDD index 2005 was used. Doses given in mono- and polytherapy were compared. RESULTS: Median PDDs in samples within the therapeutic range (in mg) in mono-/polytherapy were as follows (DDDs in parenthesis): carbamazepine 600/800 (1,000), clonazepam 2.0/2.0 (8), phenytoin 300/300 (300), ethosuximide -/1000 (1,250), lamotrigine 250/200 (300), phenobarbital -/200 (100), primidone 500/625 (1,250), topiramate -/300 (300), valproic acid 750/1,000 (1,500). Median PDDs in polytherapy with antiepileptics not analyzed for TDM were: gabapentin 900 (1,800), levetiracetam 1,500 (1,500), vigabatrin 1,500 (2,000). CONCLUSIONS: PDDs in monotherapy were similar or slightly lower than in combination therapy with an exception for lamotrigine, NS. The differences were significant in carbamazepine, p < 0.0001, and valproic acid, p < 0.001. Patients with plasma levels within the therapeutic range were usually treated with similar or slightly higher doses than the remainder. In polytherapy the PDDs were similar to DDDs in carbamazepine, ethosuximide, phenytoin, and topiramate in samples within the therapeutic range when difference +/- 20 per cent was considered as acceptable PDD of levetiracetam was also similar to actual DDD. In general plasma levels tended to be below the therapeutic range. The differences between PDD and DDD of antiepileptics have to be taken into account especially when utilization of different drugs is compared.     

638例次抗癫痫药血清浓度监测结果及其与临床疗效关联性分析

目的:为临床抗癫痫药物(AEDs)的合理使用提供科学参考。方法:对采用荧光偏振免疫(FPIA)法对丙戊酸钠、卡马西平、苯妥英钠、苯巴比妥进行血清浓度监测结果进行回顾性统计分析。结果:共监测638例次,359例次(56.27%)血药浓度位于治疗窗内,202例次(31.66%)低于治疗窗,70例次(10.97%)高于治疗窗,7例次(1.10%)未检出血清浓度;各AEDs血清浓度位于治疗窗的比例分别为卡马西平78.65%、苯巴比妥60.00%、丙戊酸钠57.48%、苯妥英钠23.08%,其中卡马西平、丙戊酸钠、苯妥英钠血清浓度位于治疗窗内癫痫治疗有效率分别为72.86%、90.57%、94.44%,明显高于其他浓度范围(χ2卡马西平=6.324,P卡马西平=0.012;χ2丙戊酸钠=122.782,P丙戊酸钠=0.000;χ2苯妥英钠=19.584,P苯妥英钠=0.000),而苯巴比妥在各浓度范围有效率差异无统计学意义(χ2=3.403,P=0.065);53例次联合用药中,12例次血清浓度在治疗窗内,占联合用药例次的22.64%。结论:对癫痫患者进行血清浓度监测,实施个体化给药,对促进抗癫痫药物安全、有效、合理使用具有重要意义。     

Extended-release formulations for the treatment of epilepsy

This review analyses the concept of extended-release (ER) formulations in epilepsy and evaluates ER formulations of carbamazepine, valproic acid and a modified-release (MR) formulation of oxcarbazepine. ER formulations are usually designed to reduce dose frequency and maintain relatively constant or flat plasma drug concentration. It is questionable whether flat plasma concentrations of an antiepileptic drug (AED) improve antiepileptic efficacy compared with fluctuating plasma concentrations. More certainly, they minimise concentration-related adverse effects, and the dosing flexibility and consistency of plasma concentrations may simplify the management of antiepileptic drug therapy. Neurologists would like ER formulations that can be administered once- and/or twice-daily to tailor therapy for the individual patient; however, switching dosage schedules from multiple dosages per day to once daily, although more convenient, will not generally improve therapeutic coverage (maintenance of effective drug concentration in biological fluids and tissue). Pharmacokinetically, the impact of a missed dose is greater the larger the dose and the less frequent the administration. Therefore, the risk of breakthrough seizure is higher during AED once-daily administration than twice-daily administration. Consequently, the increased compliance observed with fewer dosages per day should be weighed against the impact or forgiveness of omitted dose(s) and the shorter 'forgiveness' period associated with once-daily administration. Currently, the trend is to treat patients with epilepsy with ER formulations because of the better compliance, convenience and flat plasma concentration versus time curve. Thus, it seems that the term 'flatter is better' for AED plasma profiles has precipitated in the last 10-15 years among neurologists and epilepsy caregivers, and is being promoted by marketing forces of pharmaceutical companies. Data from the literature support the trend to treat epileptic patients with twice-daily administration of the existing ER formulations of valproic acid and carbamazepine, and oxcarbazepine-MR; however, the author of this article is not convinced that these ER formulations can guarantee a complete therapeutic coverage throughout the 24-hour dosing interval following once-daily administration.Epilepsy is a single-episode disease, and the convenience and possible better compliance associated with once-daily administration must be weighed against the shorter 'forgiveness' period and possible higher risk of breakthrough seizure due to sub-therapeutic plasma levels and/or omitted doses. Data suggest just a small difference in compliance between once- and twice-daily administration, with no significant difference in efficacy. Therefore, the increased compliance following once-daily administration may be counter-productive in minimising the occurrence of sub-therapeutic drug concentrations. Weighing up the advantages and disadvantages for once- versus twice-daily administration of ER formulations in epilepsy leads to a conclusion in favour of twice-daily administration.     

The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation

Aim:

To study the effects of delayed and missed doses (poor compliance) on the pharmacokinetics of carbamazepine (CBZ) and its main active metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese epilepsy patients using Monte Carlo simulation.

Methods:

CBZ and CBZE time-concentration profiles in various scenarios were generated based on a population pharmacokinetic study in Chinese epilepsy patients using Monte Carlo simulation. The scenarios included patients given multiple doses of CBZ that ranged from 100 to 300 mg three times daily or from 200 to 300 mg every 12 h. The therapeutic range of CBZ and CBZE for each scenario was estimated to assess the effect of delayed or missed doses and to design corresponding rescue regimens. Moreover, the impact of body weight, absorption rate and co-therapy with other antiepileptic drugs (phenytoin, phenobarbital and valproic acid) on the dosage recommendation was investigated in the event of poor compliance.

Results:

The risk for a sub-therapeutic range of CBZ and CBZE was increased in a dose-dependent manner in both two and three times daily regimens when delayed or missed doses occurred. The effects of poor compliance was less prominent on the lower daily doses compared with those on the higher daily doses. The dose recommendations, in the event of poor compliance, were time related and dose dependent. Patient body weight, absorption rate and co-therapy with phenytoin, phenobarbital and valproic acid had no significant impact on the dose recommendation.

Conclusion:

Patients with epilepsy should take the delayed doses as soon as they remember, and partial missed doses may need to be taken near or at the next scheduled time.     

Detection of a drug–drug interaction on population-based phenobarbitone clearance using nonlinear mixed-effects modeling

Objective: Nonlinear mixed-effects modeling (NONMEM) was used to estimate the effects of drug–drug interaction on phenobarbitone clearance values, using 648 serum levels gathered during the routine clinical care of 349 pediatric and adult epileptic patients (age range, 0.4–33.3 years). Patients received phenobarbitone as monotherapy or in combination with either of the antiepileptic drugs carbamazepine or valproic acid. Results: The final model describing phenobarbitone clearance was CL = 52.3 · TBW^–0.567 · CO, where CL is clearance (ml · kg⁻¹ · h⁻¹), TBW is total body weight (kg) and CO is a scaling factor for concomitant medication with a value of 1 for patients on phenobarbitone monotherapy, 46.4^(−1/TBW)for those patients receiving concomitant carbamazepine and 0.642 for those patients receiving concomitant valproic acid. Phenobarbitone CL was highest in the very young and decreased in a weight-related fashion in children, with minimal changes observed in adults. This pattern was consistent whether phenobarbitone was administered alone or coadministered with carbamazepine or valproic acid. When phenobarbitone was coadministered with carbamazepine or valproic acid, phenobarbitone CL decreased compared with that in monotherapy. Its magnitudes in the presence of carbamazepine are maximal in early childhood (about 54%) and decreased in a weight-related fashion in older children, with minimal changes observed in adults. Concomitant administration of phenobarbitone and valproic acid resulted in a 35.8% decrease of phenobarbitone CL. Received: 17 February 1997 / Accepted in revised form: 21 October 1997     

抗癫痫中成药中非法添加西药成分的血药浓度监测分析

目的：对长期服用抗癫痫中成药的患者进行血药浓度监测,查明抗癫痫中成药中非法添加的西药成分。方法：通过全自动生化分析仪,采用酶联免疫法测定中成药中添加的丙戊酸、卡马西平、苯巴比妥、苯妥英的种类及血药浓度。结果：所有服用抗癫痫中成药的患者中均检测到上述四种西药成分,其中含丙戊酸17例,血药浓度在有效范围内占23.53%;含卡马西平17例,血药浓度在有效范围内占17.65%;含苯巴比妥17例,血药浓度在有效范围内占41.18%;含苯妥英5例,血药浓度在有效范围内占60.00%。结论：本方法操作简便、准确,可快速筛查抗癫痫中成药中非法添加的西药成分,便于临床指导患者合理用药。     

Detection of Carbamazepine-induced Changes in Valproic Acid Relative Clearance in Man by Simple Pharmacokinetic Screening

Selecting the optimum dose of valproic acid is difficult because the pharmacokinetics are complicated by inter-patient variability and by effects arising as a result of co-administration with other antiepileptic drugs. The multiple peak approach has been used to evaluate the effect of age, total body weight, dose, gender and co-medication (carbamazepine-induced change) on population estimates of valproic acid relative clearance. Routine clinical pharmacokinetic data (n = 479) were collected from 207 epilepsy patients on combination therapy. The data were analysed by a simple steady-state pharmacokinetic model with the use of NONMEM, a computer program designed for population pharmacokinetic analysis that enables pooling of data. NONMEM estimates suggested that the rate of valproic acid clearance in patients receiving concomitant administration of valproic acid and carbamazepine decreased non-linearly with increasing total body weight in the maturation process, and increased non-linearly with increasing valproic acid dose. The clearance in females was 5.7% less than in males. NONMEM estimates also suggested that the rate of valproic acid clearance increased non-linearly with increasing carbamazepine dose. Concomitant administration of valproic acid and carbamazepine with other antiepileptic drugs resulted in an increase in valproic acid clearance of 10%. The final regression model of valproic acid relative clearance was CL = 606TBW^0.168 ×DOSE^0.414 × CBZDOSE^0.095 × 0.943^GEN × 1.10^CO, where CL is the clearance (mL kg^? h^?), TBW is the total body weight (kg), DOSE is the dose of valproic acid, CBZDOSE is the dose of carbamazepine, GEN = 0 for males and 1 for females and CO = 0 for concomitant administration of valproic acid and carbamazepine and 1 for concomitant administration of valproic acid and carbamazepine with other antiepileptic drugs. This technique can be used to estimate the pharmacokinetic parameters of a population from sparse data collected during routine clinical care and to determine the extent to which patient characteristics influence drug pharmacokinetics.     

我院2009年抗癫痫药物血药浓度监测结果分析

目的:促进临床合理应用抗癫痫药物并提高其疗效。方法:回顾性分析我院2009年门诊或住院患者服用丙戊酸(VPA)、卡马西平(CBZ)、苯妥英钠(PHT)的487例癫痫患者的血药浓度监测结果。结果:487例监测中,248例(50.92%)在有效血药浓度范围内;177例(36.34%)低于有效血药浓度;51例(10.47%)高于有效血药浓度;11例(2.26%)未检出血药浓度。其中,在有效血药浓度范围内的3种药物比例分别是VPA(48.18%)、CBZ(74.29%)、PHT(10.87%)。结论:抗癫痫药物的血药浓度监测为临床设计个体化给药方案提供了依据,是保证安全、有效用药的重要措施。     

Effect of heating human sera at a temperature necessary to deactivate human immunodeficiency virus on measurement of free phenytoin, free valproic acid, and free carbamazepine concentrations.

Minimizing the risk for infection to laboratory staff from a contaminated blood sample is a major safety goal in the clinical laboratory. One dangerous pathogen, the human immunodeficiency virus (HIV), can be deactivated by heating sera at 56 degrees C for 30 minutes. The authors previously reported that if serum was subjected to those conditions, the concentrations of the nine most commonly monitored drugs were not altered, whereas phenytoin and carbamazepine concentrations were reduced slightly. Monitoring free phenytoin, free valproic acid, and free carbamazepine concentrations is strongly recommended for patients with uremia, liver disease, and hypoalbuminemia. Because drug protein binding can be affected by temperature, the authors investigated the effect on free drug concentrations of sera heated to levels necessary for deactivation of the HIV virus. They measured total and free drug concentrations in serum pools prepared from patients receiving phenytoin, valproic acid, and carbamazepine. Serum pools were heated at 56 degrees C for 30 minutes and then brought to room temperature. The total and free drug concentrations were measured immediately after heating and then at 20- and 45-minute intervals. The concentrations of free phenytoin and free valproic acid were significantly higher after heat treatment. However, after equilibration of sera at room temperature for 20 minutes, the free concentrations of phenytoin were comparable to preheating values, although total phenytoin concentrations (Serum Separator Tubes) were reduced slightly. In contrast, free valproic acid concentrations did not return to the original levels even after 45 minutes. Free carbamazepine concentrations did not change even immediately after heating. However, total carbamazepine concentrations were reduced slightly when sera were heated in serum separator tubes (SST Tubes).     

Sampling time and indications appropriateness for therapeutically monitored drugs at a teaching university hospital in Oman

Objective: To evaluate prospectively the appropriateness of indications, sampling time and outcome of TDM requests at a teaching university hospital in Oman. Methods: A prospective cross-sectional study was conducted over a four months period; October 2013–January 2014 at the Sultan Qaboos University Hospital (SQUH), an 855 bed university teaching hospital. Appropriateness criteria for indications and sampling time were defined a priori. The evaluated drug’s requests were for carbamazepine, phenytoin, phenobarbital, valproic acid, digoxin, gentamicin, amikacin, vancomycin, tobramycin, theophylline, lithium, and cyclosporine. Results: Of 733 evaluated TDM requisitions, the majority were for antibiotics (75.0%) followed by antiepileptics (10.5%) and cyclosporine (8.9%). Most of the requests had appropriate indication (78.2%), however, only 28.5% had appropriate sampling time. Results were applied by dosage adjustments in 65.8% of requests and some of the inappropriately sampled requests (15.3%) were used as a basis for modifying the dosage regimen. Of all the reported plasma concentrations 42.3%, 41.2%, and 16.5% were within, below and above the reference range, respectively. Conclusion: TDM service is much less than optimal in SQUH. A lot of effort needs to be carried out to improve TDM use in the developing countries as adjusting the doses on results that are based on wrong sampling time might expose patients to toxicity or therapeutic failure.     

2014～2015年我院抗癫痫药物血药浓度监测结果分析

目的：通过对103例抗癫痫药物血药浓度监测结果的分析,为临床合理用药提供参考。方法采用超高效液相色谱法测定卡马西平、丙戊酸钠、苯妥英钠、奥卡西平的血药浓度,并对结果进行分析。结果卡马西平、丙戊酸钠、苯妥英钠、奥卡西平在有效血药浓度范围内分别为39例（92．3％）,19例（54．3％）,33例（12．1％）,9例（69．2％）。结论抗癫痫药物血药浓度监测对合理用药有重要的指导意义。血药浓度个体差异较大,影响因素较多,应结合其他临床指标综合分析监测结果。