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Biomedical subjects

K S Oles

Publications and source records attributed to K S Oles.

At least 19 recordsLinked to original sources
PubMed1996

Serum lamotrigine analysis by capillary electrophoresis.

Lamotrigine, a new antiepileptic drug, is analyzed by capillary zone electrophoresis. Samples were deproteinized with acetonitrile containing an internal standard, acidified with dilute acetic acid and injected into the capillary. The drug migrated rapidly with the cationic compounds in about 3.5 min far from any interfering substances. The test was linear between 0.5-10 mg/l. The analysis time was about 5 min. The CE values correlated well with an HPLC method (r = 0.97; n = 35). The mean serum concentration of 121 patients on this drug was 3.7 mg/l. Incubating the serum with beta-glucuronidase for 1 h increased the peak height of lamotrigine by about 24%.

Anticonvulsants↗
PubMed1996

Acetazolamide in the treatment of seizures.

OBJECTIVE: To summarize the pharmacology, pharmacokinetics, efficacy, and safety of acetazolamide and to evaluate its therapeutic role in patients with epilepsy. DATA SOURCES: A computerized search of the MEDLINE (OVID) database (1966-1994) was used to identify publications regarding acetazolamide. The MEDLINE search was supplemented by information from textbooks. STUDY SELECTION: Included were English-language review articles, clinical trials, cohort studies, and case reports. Topics investigated included basic pharmacology, therapeutics, toxicology, adverse reactions, dosage, administration, and pharmacokinetics of acetazolamide. DATA SYNTHESIS: Acetazolamide, a carbonic anhydrase inhibitor, has been approved for the treatment of epilepsy since 1953. Acetazolamide is primarily used in combination therapy with other antiepileptic medications in both children and adults although it may be used as monotherapy. Drug concentration monitoring has not been found to be routinely beneficial. Adverse effects include kidney stones, metabolic acidosis, lethargy, appetite suppression, paresthesias, and rare blood dyscrasias. Partial tolerance may develop to the antiepileptic activity. CONCLUSIONS: Acetazolamide is a beneficial adjunctive agent in the pharmacotherapy of epilepsy and should be considered in refractory epilepsy. Although it may be useful in partial, myoclonic, absence, and primary generalized tonic-clonic seizures uncontrolled by other marketed agents, acetazolamide has been inadequately studied by current standards and its use has been limited.

Acetazolamide↗
PubMed1994

Felbamate measured in serum by two methods: HPLC and capillary electrophoresis.

We have developed two methods for determining serum concentrations of felbamate, a new anticonvulsant drug. The first method is based on protein precipitation with acetonitrile, followed by HPLC. The between-run CV for this method is 5.7% (mean 55 mg/L), and the linearity extends from 5 to 175 mg/L. Results by this method compared well with those by an HPLC method based on chloroform extraction (r = 0.98, n = 21). In the second method, based on micellar electrokinetic capillary chromatography, the drug is measured by capillary electrophoresis with direct injection of serum. This method can be completed in 5 min compared with 12 min for the HPLC method, and there is no need for sample extraction. The between-run CV is 5.2% (mean 58 mg/L) and the linearity range is 5-160 mg/L. Results of this direct method correlated well (r = 0.98, n = 37) with those by the HPLC assay. The mean trough serum concentration of felbamate in 123 patients taking this drug was 44.9 mg/L (range 12-129 mg/L).

Acetonitriles↗
PubMed1992

Relationship between serum concentration and dose of valproic acid during monotherapy in adult outpatients.

The relationship between serum concentration and dose of valproic acid (VPA) is reported to be variable and inconsistent. However, studies evaluating this relationship have included individuals of varying ages and patients receiving potentially interacting medications. In this study, the relationship between VPA serum concentration and dose was evaluated in a homogeneous patient population. Medical records of 60 adult outpatients with epilepsy receiving VPA monotherapy were examined retrospectively for VPA dose (milligrams per kilogram) and corresponding serum VPA concentrations. A significant linear correlation was found in the relationship between VPA dose and serum concentration among all patients (r = 0.63; p less than 0.01). However, considerable interindividual variability in this ratio was demonstrated [coefficient of variation (CV) = 28.9%], and the ratio was significantly dependent on VPA dose. In three selected individual patients, a significant linear correlation was also demonstrated in the VPA serum concentration:dose relationship over time (r = 0.91, 0.94, 0.96; p less than 0.05 for all three patients) with substantially less variability (CV = 10.2-14.6%) and without significant dose dependency, suggesting that this parameter may be useful for guiding VPA dosage adjustment and monitoring patient compliance. Further study is required to evaluate the utility of the serum concentration:dose ratio in monitoring VPA therapy.

Adult↗
PubMed1992

Therapeutic bioequivalency study of brand name versus generic carbamazepine.

We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency.

Adolescent↗
PubMed1992

Serum and tissue carnitine assay based on dialysis.

Carnitine (L-beta-hydroxy-gamma-trimethylaminobutyric acid) aids mitochondrial energy production by transferring fatty acids across the membranes for beta-oxidation. We describe here a modified enzymatic assay for free serum and tissue carnitine based on dialysis to remove interfering substances in the serum, with subsequent conversion of carnitine to the acyl derivative by carnitine acetyltransferase (EC 2.3.1.7) in the presence of 5,5'-dithiobis-(2-nitrobenzoic acid). The method compared well with a radioenzymatic assay. The reference interval for serum is 28-70 mumol/L. Patients with advanced diabetes and those undergoing valproic acid treatment displayed lower mean values; a statistically significant number of them showed serum carnitine values below the reference interval. The method was also applied to carnitine measurement in cerebrospinal fluid and human tissues.

Carnitine↗
PubMed1990

Therapeutic drug monitoring analysis systems for the physician office laboratory: a review of the literature.

Commercially available systems for therapeutic drug monitoring in the physician office laboratory (POL) are reviewed. The Abbott Vision, Kodak Ektachem, Syntex AccuLevel, Syva Emit QST, Ames Seralyzer ARIS, and Ames Clinimate ARIS have been found to be sensitive and accurate compared with more conventional laboratory assays, and are well-suited for the POL. The number of available drug assay is very limited with every system except the QST. The QST offers a large menu and would be appropriate for large practices. The Abbott TDx or other semiautomated system usually found in the clinical chemistry laboratory may be particularly useful and cost-effective in office practices with a large volume of specimens. AccuLevel or ARIS might be the best choices for clinics or pharmacies that generate few samples. The start-up time is the longest with the Vision and Ektachem systems (30 minutes). Most systems have the capacity to produce results within one to five minutes with the exceptions of the Vision (13 minutes for theophylline) and AccuLevel (20 minutes). The Vision is the most automated system and both AccuLevel and the Vision use whole blood, thereby bypassing the additional time required for centrifugation of the patient specimen. The Ektachem, Vision, and QST have an operator-independent pipetting step that offers a significant advantage when operated by semiskilled personnel. Although the AccuLevel eliminates the need for a large initial capital expenditure, the individual cost per test is higher. Leasing programs are available or certain systems. Increased government regulation will improve the quality control of therapeutic drug monitoring in the POL.

Clinical Laboratory Techniques↗
PubMed1990

The effect of hemodialysis and hemoperfusion on serum valproic acid concentration.

We report a patient with dialysis-induced encephalopathy who was taking divalproex sodium for a seizure disorder. Her serum valproic acid concentration appeared to be in the low therapeutic range at 54 mg/l yet she continued to have seizure activity. The elimination half-life and apparent clearance of valproic acid were the same for both a dialysis and nondialysis day, indicating that hemodialysis/hemoperfusion has little effect on the overall removal of valproic acid from the body.

Female↗
PubMed1989

Catastrophic neurologic signs due to drug interaction: Tegretol and Darvon.

Eight cases of carbamazepine toxicity from interaction with propoxyphene are reported. Serum concentrations of carbamazepine increased up to sixfold. All patients were symptomatic and two were hospitalized. Practitioners prescribing propoxyphene acutely for pain should be aware of this significant interaction.

Adult↗
PubMed1989

Carbamazepine clearance in hemodialysis and hemoperfusion.

A 47-year-old woman with endstage renal disease and dialysis-induced encephalopathy was being treated with carbamazepine for myoclonus. Her carbamazepine serum concentration appeared to be therapeutic at 5.1 micrograms/ml. She experienced a seizure while on hemodialysis/hemoperfusion that was possibly related to the removal of carbamazepine during dialysis. The elimination of carbamazepine on a dialysis day was compared with elimination on a nondialysis day. The half-life and apparent clearance were the same for each day, indicating that hemodialysis/hemoperfusion had little effect on the overall removal of carbamazepine from the body. The possible reasons for this lack of effect are discussed.

Carbamazepine↗
PubMed1989

Phenytoin and phenobarbital concentrations in serum: a comparison of Ames Seralyzer with GLC, TDX, and EMIT.

A recently developed system for measuring antiepileptic drug concentrations was evaluated for phenytoin and phenobarbital. The apoenzyme reactive immunoassay system was compared with gas-liquid chromatography, EMIT, and TDX systems. Comparisons were performed with control specimens and with sera obtained from patients at three facilities. Precision for all methods was similar, with within-run and between-run coefficients of variation generally 5%. The accuracy of all methods was acceptable, but bias was present in some. However, measurements obtained by a nontechnical person (physician) in a clinical setting were sometimes inaccurate.

Chromatography, Gas↗
PubMed1989

Evaluation of an enzyme immunochromatography method for carbamazepine: a comparison with enzyme-multiplied immunoassay technique, fluorescence polarization immunoassay, and high-performance liquid chromatography.

A noninstrumented enzyme immunochromatography (EIC) method for monitoring carbamazepine using whole blood was compared to the enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA), and high-performance liquid chromatography (HPLC). Samples from 74 patients were evaluated in the comparison study, yielding correlation coefficients of 0.961 (EMIT), 0.974 (FPIA), and 0.867 (HPLC). The EIC method produced within-run coefficients of variation of 4.3%, 4.9%, and 5.8% for three carbamazepine concentrations. The between-run coefficient of variation over 107 days was 4.9%. The spiked serum sample analysis yielded recovery rates ranging from 98 to 102%. Enzyme immunochromatography was found to be a useful noninstrumented method for on-site testing. The test gives quantitative patient sample results comparable to the results obtained using established laboratory methods.

Adolescent↗
PubMed1988

Valproic acid efficacy, toxicity, and pharmacokinetics in neonates with intractable seizures.

Six neonates with prolonged, intractable seizures were treated with valproic acid (VPA). Each patient had received maximum doses of phenobarbital (greater than 40 micrograms/ml), and five patients received at least two additional anticonvulsants, without success. Seizure activity was controlled in five of six (83%) cases. In four cases, all other anticonvulsants could be withdrawn, and seizures were controlled on VPA monotherapy. VPA was discontinued in three patients because of VPA-induced hyperammonemia. VPA pharmacokinetic measurements were as follows: for total VPA, volume of distribution (V) = 0.40 l/kg (range, 0.36 to 0.47 l/kg), serum clearance (Cl) = 14.4 ml/h/kg (5.5 to 18.2 ml/h/kg), half-life (T1/2) = 26.4 hours (8.6 to 48.5); for unbound VPA, V = 2.02 l/kg (1.14 to 2.44 l/kg), Cl = 108.9 ml/h/kg (42.0 to 252.0 ml/h/kg). T1/2 = 17.6 hours (6.7 to 34.2). VPA free fraction ranged from 11.3 to 31.6% (mean, 19.2%).

Absorption↗
PubMed1984

Hyponatremia induced by thiazide-like diuretics in the elderly.

We have presented five episodes of hydrochlorothiazide-induced hyponatremia in three elderly nursing home patients. Fortunately all our patients survived. The common use of thiazide diuretics in this population and the nonspecific symptoms that follow toxicity make it imperative to monitor closely elderly patients who are taking thiazide diuretics.

Aged↗
PubMed1984

The role of the pharmacist in a geriatric nursing home: a literature review.

This review delineates the pharmacist's controversial clinical role in nursing homes as it has developed within the legal, social, and economic climate of the Medicaid and Medicare conditions of participation. Special problems of the geriatric institutionalized patient include polypharmacy, adverse reactions, the overuse of prn drugs, and inadequate physician contact. These problems are compounded by an impoverished scientific data-base for appropriate drug use in the aged. Studies that clarify the impact consultant pharmacists have on the number of drugs prescribed, adverse reactions, and cost containment are compiled and evaluated. It is shown that pharmacists can reduce the number and cost of drugs. Physician acceptance of pharmacists' recommendations was found to be at least 60 percent in these reports. Well-controlled studies are lacking in the literature.

Aged↗
PubMedDate not supplied

Use of acetazolamide as an adjunct to carbamazepine in refractory partial seizures.

Acetazolamide (Diamox) (AZM) was evaluated as an adjunct to carbamazepine (CBZ) monotherapy in 48 refractory partial seizure patients at a tertiary care referral center. Patient ages ranged from 6 to 64 years (average 28 years). Seizure frequencies for the pre-AZM baseline period (CBZ monotherapy) were compared with the seizure frequencies at different daily doses of AZM. Patients with a 50% decrease in seizure frequency were considered responders. Twenty-one patients were responders (44%) and three became completely seizure-free. Effective doses ranged from 3.8 to 22.0 mg/kg/day. Effective plasma concentrations ranged from 1 to 22 micrograms/ml in selected patients. Durations of response time to AZM ranged from 3 to 30 months (average 12.9 months). Three patients lost response, one temporarily. Side effects were seen in 10 patients, requiring discontinuation in three.

Acetazolamide↗