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Biomedical subjects

H Kutt

Publications and source records attributed to H Kutt.

At least 37 records · Page 2Linked to original sources
PubMed1987

Controlled-release levodopa/carbidopa. II. Sinemet CR4 treatment of response fluctuations in Parkinson's disease.

Sixteen patients with Parkinson's disease and therapeutic response fluctuations entered an open-label trial of a controlled-release carbidopa/levodopa preparation, Sinemet CR4. Sinemet CR4 behaved as a slow release preparation. At the end of 6 weeks CR4 treatment, there was an increase in percent "on" time and mean interdose interval; the number of daily doses and "off" periods were diminished and a slight reduction in the variability of plasma levodopa levels was observed. Overall benefit waned over the next 6 months, despite addition of standard levodopa or Sinemet to overcome the delayed onset of antiparkinsonian effect of CR4 which resulted from prolongation in the Tmax for levodopa. The major benefits of CR4 were reduction in off time and in the number of daily off periods, with fewer levodopa doses per day and prolongation of the interdose interval.

Carbidopa↗
PubMed1987

Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease.

Eight Parkinson patients with response fluctuations completed an open-label trial of a controlled-release carbidopa/levodopa preparation (Sinemet CR3). At the end of 6 weeks, percent "on" time and mean interdose interval increased, the number of daily doses and "off" periods was decreased, and the variability of plasma levodopa levels and disability scores was reduced. However, response fluctuations continued to occur, day-to-day consistency was poor, and the bioavailability of levodopa appeared less than that of standard Sinemet. Overall benefit waned over the next 3 to 6 months. Oral controlled-release carbidopa/levodopa is capable of reducing fluctuations in plasma levodopa levels and clinical performance in Parkinson's disease. The response to this particular controlled-release formulation was suboptimal and unsustained.

Adult↗
PubMed1986

Effect of supplemental carbidopa on bioavailability of L-dopa.

The effect of doubling carbidopa intake on single dose bioavailability of L-Dopa was examined in five parkinsonian patients. Increasing carbidopa from a mean of 145 to 290 mg/day caused a mean increase in peak plasma Dopa concentrations from 1,893 +/- 476 to 2,733 +/- 607 ng/ml and area under the Dopa plasma concentration versus time curve of 24.6 +/- 10.0%, as well as a decrease in the time to peak plasma concentration to 0.7 +/- 0.2 versus 1.2 +/- 0.3 h. Increasing the within-dose ratio of carbidopa to L-Dopa, even in patients receiving "maximally effective" doses of carbidopa, further increases bioavailability of L-Dopa, presumably by inhibiting "first pass' metabolism in the gut.

Aged↗
PubMed1985

Plasma 10-hydroxynortriptyline and ECG changes in elderly depressed patients.

Among 18 elderly depressed patients given ECGs before and during nortriptyline treatment, plasma E-10-hydroxynortriptyline and the sum of E-10-hydroxynortriptyline and nortriptyline distinguished the group with conduction/repolarization effects. Plasma nortriptyline, age, drug dose, and baseline cardiovascular status did not.

Age Factors↗
PubMed1985

Drug interactions between antiepileptic drugs and other drugs.

Antiepileptic drugs interact with a variety of other drugs to affect the pharmacokinetic behavior of either drug. Drug interactions may also occur when antiepileptic drugs are given in combination. The possibility of such interactions is not a contraindication to the use of combinations, but it requires that the clinician be aware of the problem and monitor patients given potentially interacting combinations.

Anticonvulsants↗
PubMed1984

Plasma 10-hydroxynortriptyline in elderly depressed patients.

Plasma concentrations of nortriptyline (NT) and of unconjugated E-10-hydroxynortriptyline (E-10-OH-NT) were measured under steady-state conditions in elderly (60 yr and older) and young adult (40 yr and younger) patients treated with NT. The two groups received equivalent doses of NT. Plasma NT concentrations of the two groups did not differ, but plasma E-10-OH-NT concentrations were higher in the elderly. The plasma E-10-OH-NT/NT ratios were twice as high in the elderly group. Plasma E-10-OH-NT/NT ratios varied 2000% between individuals in the elderly group but were stable within individuals. Plasma E-10-OH-NT/NT ratios correlated positively but weakly with serum creatinine concentrations.

Adolescent↗
PubMed1984

Enhanced gastrointestinal excretion of phenytoin in a patient with Crohn's disease.

A patient with Crohn's disease and generalized seizures who lacked the distal small bowel and ascending colon required 600 mg of intravenous phenytoin daily (11 mg/kg/24 h) to maintain her plasma phenytoin levels in the 12-24 micrograms/ml range. She received no oral phenytoin. Stool volumes ranged from 1,125 to 1,875 ml/24 h, and stool fraction phenytoin levels from 15 to 41 micrograms/ml. Urinary 5-(p-hydroxyphenyl)-5-phenylhydantoin and phenytoin levels in three 24-h samples were sufficient to account for 26, 46, and 57% of the administered drug, compared with the expected 70-90%. This was most likely due to an alteration of the normal cycle of absorption and reexcretion between the intestinal lumen and the blood resulting in net excretion of phenytoin into the bowel.

Adult↗
PubMed1984

Interactions between anticonvulsants and other commonly prescribed drugs.

Many drug interactions can be demonstrated, but only a few are so clinically significant that they necessitate adjusting drug dosages. The same drug combination may produce changes of variable extent or direction in different individuals. The reasons for this variability include genetic control of the rate and inducibility of drug metabolism, and environmental factors such as contact with chemicals. Among antimicrobial agents, chloramphenicol may cause accumulation of phenytoin (PHT) and phenobarbital (PB), and isoniazid may cause PHT, carbamazepine (CBZ), and primidone (PRM) to accumulate. Erythromycin may cause accumulation of CBZ. Among anti-ulcer agents, antacids may reduce PHT concentration while cimetidine may cause accumulation of PHT, CBZ, and diazepam (DZP). Salicylates displace strongly binding drugs such as PHT, DZP, or valproate (VPA) from the binding sites in plasma proteins, which may lead to some decline of the total plasma level with an increase in the unbound drug percentage. Conversely, anticonvulsants may influence the dosage requirements of oral anticoagulants by inducing their metabolism. Failures of oral contraceptives have been attributed to anticonvulsants in some patients. Probably the most predictable interaction that necessitates dosage adjustment is accumulation of PB caused by VPA. Intentional inhibition of PRM metabolism by nicotinamide serves as an example of attempts to utilize an interaction for improved therapeutic effect.

Analgesics↗
PubMed1984

Improved liquid-chromatographic determination of haloperidol in plasma.

This method for determination of haloperidol in plasma is based on "high-performance" isocratic liquid chromatography with the use of a C8 bonded reversed-phase column at room temperature. Haloperidol and the internal standard (chloro-substituted analog) are extracted from alkalinized plasma into isoamyl alcohol/heptane (1.5/98.5 by vol) and back-extracted into dilute H2SO4. The aqueous phase is directly injected onto the column. The mobile phase is a 30/45/25 (by vol) mixture of phosphate buffer (16.5 mmol/L, pH 7.0), acetonitrile, and methanol. Unlike other liquid-chromatographic procedures for haloperidol, commonly used psychotropic drugs do not interfere. Analysis can be completed within an hour. The procedure is extremely sensitive (1.0 microgram/L) and is well reproducible (CV 5.6% for a 2.5 micrograms/L concentration in plasma).

Child↗
PubMed1982

Determination of diazepam and its pharmacologically active metabolites in blood by bond Elut column extraction and reversed-phase high-performance liquid chromatography.

A rapid and quantitative analytical micro method for the determination of diazepam and its major pharmacologically active metabolites utilizing high-performance liquid chromatography (HPLC) is reported. The drug and its metabolites were extracted from 50-100 microliter samples of whole blood, serum or plasma using Bond Elut C 18 column and quantitated by high-performance liquid chromatography, using Technician Fast-LC-C-8 (RP 5 micrometers) bonded column and a mobile phase consisting of 53% methanol, 1% acetonitrile in KH2PO4 buffer and 10 microliters/l triethylamine. Methyl nitrazepam and medazepam were used as internal and external standards respectively. The extraction and recovery of diazepam and its major pharmacologically active metabolites, i.e., 3-hydroxydiazepam, desmethyldiazepam and oxazepam from blood were higher than 88% for all compounds. The minimum detection range of each compound was approximately 2.5 ng per 100-microliter sample. This micro method of simultaneous quantitation of diazepam and its major pharmacologically active metabolites provides a valuable technique for the study of diazepam pharmacokinetics in a small animal model without disturbance of normal hemodynamics from excess blood loss, as well as in clinical evaluation of pediatric patients.

Chromatography, High Pressure Liquid↗
PubMed1981

Improved gas chromatographic procedure for the determination of clonazepam levels in plasma using a nitrogen-sensitive detector.

A gas-liquid chromatographic procedure (GLC) is described for the determination of clonazepam in plasma. The drug is extracted from buffered plasma at pH 9.0 with diethyl ether and then back-extracted into 6 N hydrochloric acid-6N sulfuric acid (95:5) and hydrolyzed at 100 degrees C to convert the drug into its benzophenone derivative. The benzophenone derivative of flurazepam is added to plasma as an internal reference standard. Drug derivatives are finally extracted from the neutralized aqueous phase and assayed by GLC. The present procedure makes use of a nitrogen-sensitive detector which is more stable and selective than the commonly employed electron-capture procedure. The sensitivity of the detector for clonazepam is 1 ng/ml.

Anticonvulsants↗
PubMed1980

A comparison of plasma phenytoin level determinations by EMIT and gas-liquid chromatography in patients with renal insufficiency.

Monitoring the blood levels of antiepileptic drugs (AED) has proven to be of value in the clinical management of epileptic patients. We have compared the plasma concentrations of AED determined by enzyme multiplied immunoassays (EMIT) and gas-liquid chromatography (GLC) assays and identified a group of patients (n = 22) in whom the EMIT values for phenytoin were up to three times higher than those obtained by GLC. All these patients were oliguric with various degrees of azotemia, most of them undergoing weekly hemodialysis. The ratio of EMIT over GLC was 2.0 in 14 patients, 2.5 in 5 patients, and near 3.0 in 3 patients. These ratios remained relatively constant during repeated determinations over several months. The magnitude of difference between EMIT and GLC values (microgram/ml) was not related to the degree of azotemia. The discrepancy remained unchanged when various modifications of EMIT and GLC techniques were used. When phenytoin was added in vitro to plasma from nonepileptic oliguric azotemic patients, the measured phenytoin values were close to and not higher than the target values by either methodology. We feel that, when monitoring phenytoin blood levels in epileptic patients with renal insufficiency, one should be aware of a discrepancy between phenytoin values assayed by GLC and EMIT.

Chromatography, Gas↗