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Biomedical subjects

H Kutt

Publications and source records attributed to H Kutt.

At least 19 recordsLinked to original sources
PubMed1998

Feasibility and pharmacokinetics of carbamazepine oral loading doses.

The pharmacokinetics and adverse effects of an oral loading dose of carbamazepine administered in tablet or suspension form were studied. Patients on a hospital epilepsy unit who were to receive carbamazepine as a discharge medication were randomly assigned to receive either an oral 8-mg/kg loading dose of the tablet formulation or the same dose of the suspension on an empty stomach. Blood samples were drawn before and at intervals up to 12 hours after the loading dose. Adverse effects were evaluated subjectively and objectively. Total and free serum carbamazepine and carbamazepine-10, 11-epoxide (CBZE) concentrations were determined by high-performance liquid chromatography. Six adult patients were enrolled in and completed the study. All the patients achieved therapeutic total carbamazepine levels; the suspension group did so within two hours and the tablet group within five hours. Maximum serum carbamazepine concentrations ranged from 7.10 to 9.92 mg/L, area under the concentration-versus-time curve from 54.85 to 82.23 micrograms.hr/L, and terminal elimination half-life from 14.05 to 15.71 hours. Adverse effects were mild, few, and short-lived; none of the patients developed gastrointestinal toxicity. Adverse effects were not associated with total or free carbamazepine and CBZE concentrations or with total or free CBZE:carbamazepine ratios. An oral loading dose of carbamazepine 8 mg/kg achieved therapeutic levels within two hours when given as a suspension and within five hours when given as tablets and was well tolerated in all patients.

Adult↗
PubMed1996

Felbamate levels in patients with epilepsy.

The usefulness of felbamate (FBM) levels in managing epilepsy patients has not been determined. The purpose of the present study was to determine if FBM levels obtained at routine office visits correlated with side effects reported by patients. We determined FBM levels by high-pressure liquid chromatography (HPLC) of 46 epilepsy patient plasma specimens (41 patients) and assessed medication toxicity and seizure frequency by a questionnaire. Thirty-six patients were treated with other antiepileptic drugs (AEDs); concomitant AED levels not in ranges believed to cause toxicity. FBM levels ranged from 9 to 134 microgram/ml, and were divided into three groups for analysis, resulting in low-range (9-36 microgram/ml), midrange (37-54 microgram/ml), and high-level (44-134 microgram/ml) groups. Anorexia and complaints of severe side effects were reported significantly more often in the high-level group as compared with the low- and midrange groups. Significantly more patients in the high-level group (10/13) reported decreased seizure frequency, as compared with 12 of 30 patients in the low- and midrange groups combined. FBM levels correlated linearly with doses overall, but most closely in FBM monotherapy patients.

Adolescent↗
PubMed1995

3,4-diaminopyridine as a treatment for amyotrophic lateral sclerosis.

The slow potassium channel blocker 3,4-diaminopyridine (DAP) enhances acetylcholine release from the nerve terminal and improves conduction in unmyelinated nerve. In this open label pilot study, we examined the effect of DAP combined with inpatient rehabilitation in seven patients with motor weakness due to amyotrophic lateral sclerosis (ALS). A single daily 20 mg oral dose of DAP was gradually increased to the maximum tolerated dose, and serum DAP concentrations were measured. Videotaped motor examination (for subsequent "blinded" review and assignment of a quantitative motor score), Functional Independence Measure (FIM) assessment, nerve conduction studies and neuropsychological evaluations were performed on admission, 1 h after maximum DAP dose, and post-treatment. DAP was tolerated in all patients, though dose was limited by gastrointestinal side effects in five patients. The mean peak serum level was 128 (+/- 50) ng/ml, occurring 1.0 (+/- 0.50) h after dose. A modest but statistically significant (p = 0.045) peak in motor score occurred on DAP. A significant (p = 0.045) improvement from baseline in FIM performance was apparent with DAP. Nerve conduction studies showed small increases in evoked response amplitudes and conduction velocities on DAP, but they did not reach statistical significance. No cognitive or affective changes were apparent. This unblinded pilot study shows that DAP is tolerated in ALS patients, and may be associated with functional and electrophysiologic improvement.

4-Aminopyridine↗
PubMed1994

Baclofen toxicity in a patient with subclinical renal insufficiency.

Baclofen, a centrally acting gamma-aminobutyric acid agonist is a commonly used pharmacotherapy for spasticity of spinal origin. It is primarily excreted by glomerular filtration with a clearance proportional to creatinine clearance. We describe a 39-year-old quadriplegic women who, over a 16-week period, developed clinical signs of baclofen toxicity confirmed by progressively rising serum baclofen levels while on a conventional stable dosing regimen. During this period blood urea nitrogen and creatinine concentrations were normal and stable (9mg/dL and 0.8mg/dL, respectively). However, creatinine clearance values were consistently low (55 to 60m/min), suggesting renal insufficiency as the underlying cause. After a decrease in baclofen dosage, evidence of baclofen toxicity resolved. Clinicians should be alert to signs of evolving baclofen toxicity even in patients on an apparently stable regimen. Baclofen dosage adjustments based on systemic baclofen level may play a role in optimizing the clinical management of spasticity.

Adult↗
PubMed1992

Clinical and pharmacokinetic aspects of high dose oral baclofen therapy.

Baclofen is a centrally acting muscle relaxant used for treatment of spasticity. Some patients, to experience adequate symptomatic relief, require dosages of baclofen that significantly exceed the conventional 80 mg daily maximum advocated by the 1992 Physicians' Desk Reference. In this pilot study of baclofen kinetics and dynamics in eleven patients, the safety and efficacy of high dose baclofen was confirmed. The data suggest that the pharmacokinetics of high dose baclofen may vary from those described previously. Time-to-peak plasma levels and plasma half-lives were noted to be substantially longer than prior reports indicate. Baclofen blood levels were observed to rise gradually over time in some patients on a stable dosing regimen, probably a result of impaired renal clearance. These findings may indicate that a change in pattern of prescription is warranted and that a reliable and practical measurement of systemic baclofen levels has a useful role in clinical practice, particularly for the patient with neurogenic bladder and potential renal insufficiency.

Administration, Oral↗
PubMed1990

L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease.

Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily "off" periods and an increase in the portion of waking day spent "on." Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Sustained enteral administration of levodopa increases and interrupted infusion decreases levodopa dose requirements.

We placed a 60-year-old man with Parkinson's disease and marked therapeutic response fluctuations on a continuous enteral infusion of levodopa. On around-the-clock infusion, motor performance declined, although the infusion rate was progressively increased. We therefore interrupted the infusion each night. The patient could then progressively reduce levodopa intake while remaining continuously "on." Continuous infusion of levodopa downregulates, and interrupted infusion can restore, and even enhance, the sensitivity of striatal dopamine receptors.

Drug Administration Schedule↗
PubMed1989

A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100).

Seventeen patients with advanced Parkinson's disease who had fluctuations in motor performance while taking standard Sinemet (STD) 25/100 underwent daylong pharmacokinetic and clinical observation studies while taking both STD and Sinemet CR, a new controlled-release formulation containing 50 mg carbidopa and 200 mg levodopa. During treatment with Sinemet CR, there was an increase in the interdose interval, a reduction in the number of medication doses taken each day, an increase in total "on" time, and a reduction in the number of "off" episodes. Total daily levodopa intake was greater with Sinemet CR, although the bioavailability of levodopa and carbidopa from the two preparations was equivalent. The variability in plasma levodopa levels was significantly less with Sinemet CR. The slower release of drug from Sinemet CR was reflected in a prolongation of the Tmax for levodopa and a prolongation of the interval from Tmax to the succeeding trough levodopa level. Clinically, peak antiparkinsonian effect occurred later and lasted longer with the CR preparation.

Antiparkinson Agents↗
PubMed1988

Isomers of 10-hydroxynortriptyline in geriatric depression.

In geriatric, depressed inpatients treated with nortriptyline (NT), total unconjugated plasma concentrations of the Z isomer of the 10-hydroxylated metabolite (10-OH-NT) were determined simultaneously with concentrations of the E isomer by high-performance liquid chromatography. Z-10-OH-NT concentrations averaged 14% of E-10-OH-NT concentrations.

Aged↗
PubMed1988

Clinical significance of the relationship between O-methyldopa levels and levodopa intake.

A recent clinical trial of controlled-release carbidopa/levodopa preparation afforded us the opportunity to examine the effects of chronically increasing circulating 3-O-methyldopa (OMD) levels on the clinical response to levodopa. In patients taking standard Sinemet, both mean plasma OMD levels and the area under the plasma concentration-versus-time curve (AUC) obtained during 8-hour periods of blood sampling correlated highly with the total daily intake of levodopa. In patients taking the controlled-release formulation, the mean daily intake of levodopa was doubled. This, in turn, led to a doubling of the mean OMD level and its AUC, whereas the AUC for levodopa was unchanged. Despite the increase in circulating OMD there was no reduction in mobility in either the "on" or "off" conditions. Thus, doubling plasma OMD levels did not seem to interfere with brain uptake of levodopa sufficiently to cause a deterioration in its therapeutic efficacy in these patients.

Animals↗
PubMed1988

Controlled-release levodopa/carbidopa. III: Sinemet CR5 treatment of response fluctuations in Parkinson's disease.

Five patients with advanced Parkinson's disease and fluctuations in therapeutic response to levodopa participated in, and four completed, an open label study of the efficacy of Sinemet CR5. Reductions in the number of daily doses and "off" periods as well as the increase in interdose interval and percent "on" time versus standard Sinemet were comparable to those achieved with Sinemet CR4 in these same patients. As compared with Sinemet CR4, there was a greater delay in the occurrence of peak plasma levodopa concentrations, and relative bioavailability was reduced. Sinemet CR5 appears to offer no advantages over Sinemet CR4 in the treatment of response fluctuations in Parkinson's disease.

Aged↗