PubMed Health⌕ Search

Biomedical subjects

N E Larsen

Publications and source records attributed to N E Larsen.

At least 73 records · Page 4Linked to original sources
PubMed1980

Plasma levels of zimelidine and norzimelidine in endogenous depression.

A new serotonin uptake inhibitor zimelidine was studied in 16 endogenously depressed inpatients, who received 150 mg/kg orally during 3--6 weeks in a phase II-type study. Plasma concentrations of zimelidine and its main metabolite norzimelidine were determined twice a week. Ten patients obtained a well-defined steady-state plasma level within 1--2 weeks, while three patients still had increasing concentrations of both substances or only norzimelidine within the investigation period. In two patients, biochemical affection of the liver could be demonstrated during the treatment; one associated with moderate clinical symptoms (dizziness and fever), the other without clinical symptoms. Both patients recovered upon cessation of the zimelidine treatment. In the former patient, very high concentrations of zimelidine at the time of hepatic symptoms were demonstrated, while the latter patient was within the average concentration range. Other adverse reactions were mild and few, particularly with respect to anticholinergic effects. With the applied, probably suboptimal, dosage the therapeutic response was only satisfactory in five cases.

Adult↗
PubMed1980

Bromocriptine concentration in saliva plasma after long-term treatment of patients with Parkinson's disease.

Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.

Aged↗
PubMed1980

Factors influencing nortriptyline steady-state kinetics: plasma and saliva levels.

Proportionality between dose and steady-state nortriptyline (NT) plasma levels was found both during initial treatment and after long-term treatment (years) within the NT Plasma level range of 20 to 296 ng/ml. There were day-to-day variations of 10% to 20% (coefficient of variation) but no systematic changes in plasma levels over time. A significant age variation in NT plasma levels was found in 116 patients. Patients over 70 yr of age (n = 23) had higher levels than other age groups (p < 0.001) dose corrected; p < 0.0001 dose and weight corrected). It was found that during episodes of acute inflammatory diseases NT steady-state plasma levels rose after a change in sedimentation rate. Our data show that the use of saliva rather than plasma in therapeutic drug level monitoring of NT cannot be recommended because the saliva/plasma ratio varied both intra- and interindividually by factors of from 2 to 4.

Adult↗
PubMed1980

Elimination of oral cimetidine in chronic renal failure and during haemodialysis.

1 The absorption and elimination of a single oral dose of 400 mg cimetidine was studied in fourteen fasting patients with impaired renal function. In addition, the dialysance of cimetidine was studied in five patients on haemodialysis. 2 The absorption was somewhat, but clinically insignificantly delayed. A second unexplained peak in the absorption curve was found. 3 First order elimination kinetics were confirmed and the length of time of a cimetidine concentration over 0.5 mg/l could be correlated with creatinine clearance. 4 The magnitude of extra renal elimination was estimated to be approximately one fourth of total cimetidine elimination in normal patients and seemed unaffected by impaired renal function. 5 A dose schedule based on AUC found in the patients in renal failure is suggested. The recommendations for daily oral dose range from 300 mg (at borderline dialysis) to 1000 mg in mild renal failure. The suggested doses will give an average plasma concentration of the same order as seen in patients with normal renal function.

Adult↗
PubMed1979

Determination of bromocriptine in plasma: comparison of gas chromatography, mass fragmentography and liquid chromatography.

Gas chromatographic, mass fragmentographic and liquid chromatographic techniques for the determinations of bromocriptine (2-bromo-alpha-ergocriptine; Parlodel) in human plasma are described. These methods were found to be suitable for determining concentrations of bromocriptine down to 0.5, 1.0 and 10.0 microgram/l, respectively. Accuracy, specificity and analytical capacity were satisfactory for all three methods. Gas chromatography was compared with liquid chromatography, and the two methods were demonstrated to give identical results in patients treated with bromocriptine for Parkinson's disease. Gas chromatography was also compared with mass fragmentography, and the results from these two assays were also in agreement.

Bromocriptine↗
PubMed1979

Pharmacokinetics of bromocriptine during continuous oral treatment of Parkinson's disease.

The plasma kinetics of bromocriptine (BCT), a long-acting dopamine agonist, was studied in twelve patients with Parkinson's disease, using a newly developed gas chromatographic method of analysis. Each patient received BCT for at least three weeks in a constant but different dose regimen. Concomitant treatment with 1-DOPA was not allowed. During a 6-day hospitalization period, a blood sample was taken immediately before the afternoon dose at 14.00 h (Cmin) to determine the steady-state level. On the 6th day blood samples were collected every hour during two 8 h dose intervals. The results showed a significant correlation between the mean values of the AUC and the Cmin. First order elimination kinetics appeared to be followed by BCT, at least for the plasma concentrations commonly found. Considerable inter-individual variation was demonstrated both for the dose/plasma concentration ratio and for calculated plasma clearances. No serious side-effects were observed during the investigation.

Aged↗
PubMed1979

Cimetidine assay in human plasma by liquid chromatography.

An assay for the determination of cimetidine in human plasma is described. Cimetidine was extracted from alkalized plasma with ethyl acetate, washed once over hydrochloric acid, re-extracted into ethyl acetate, and the organic phase was evaporated to dryness. The residue was dissolved in ethanol and injected into a liquid chromatograph. In vitro sulphoxidation was found to occur in whole blood, for which reason the assay was performed in plasma. The accuracy of the method was found to be within 3% and the lower limit for sensitivity was demonstrated to be 0.1 mg/l using 750 microliters plasma. Five volunteers received 1 g cimetidine perorally per day given in four doses with various intervals. Blood samples were drawn hourly, five dose intervals over two days. The average minimum concentration of plasma cimetidine was found to correlate significantly with the mean value of the area under the time/concentration curve over a period of three dose intervals (r = 0.96).

Adolescent↗
PubMed1979

Plasma levels of perphenazine and its major metabolites during simultaneous treatment with anticholinergic drugs.

1. A gas chromatographic method was applied to study plasma levels of perphenazine (PPZ) and its major metabolites in man before and during simultaneous antiparkinson treatment. Twenty-six psychotic patients received various forms of PPZ administration as well as antiparkinson drugs. 2. Biperidine (5 mg) was administered intravenously to each of five patients, who 5 days earlier had had a single dose of PPZ-enanthate i.m. No significant alterations in plasma concentrations of PPZ were observed. 3. In fourteen patients receiving oral PPZ treatment the plasma levels of PPZ and its metabolites did not deviate significantly from controls after addition of biperidine or orphenadine given for 3 weeks in fixed oral doses. 4. The ratio between PPZ plasma concentration measured 4 and 7 h after the morning dose was not affected by concomitant antiparkinson therapy. 5. It is concluded that no clinically relevant pharmacokinetic interaction takes place between PPZ and two generally used antiparkinson drugs during steady-state conditions in psychotic patients.

Administration, Oral↗
PubMed1979

Saliva secretion following long-term antidepressant treatment with nortriptyline controlled by plasma levels.

Eight patients undergoing antidepressant therapy with nortriptyline for 1--4 years were investigated. The period of the investigation was 7 weeks and included a 2-week placebo period, blind for the patients. Total saliva secretion measurement, the nortriptyline plasma level, and signs and symptoms of depression and side effects were obtained once a week during the study. The results of the investigation were: (1) long-term treatment with nortriptyline is followed by hyposecretion or xerostomia, (2) the reduction of the secretion is reversible, (3) re-establishment of treatment with dosage leading to the same serum level of nortriptyline is immediately followed by a drop in saliva secretion, and (4) the changes in salivary secretion are useful as an indicator of side effects. The practical importance of the investigation is discussed.

Aged↗
PubMed1979

The influence of cimetidine on basal gastro-oesophageal sphincter pressure, intargastric pH, and serum gastrin concentration in normal subjects.

A pressure and pH-sensitive probe has been constructed for simultaneous measurement of gastro-oesophageal sphincter pressure and intragastric pH. The coefficient of variation for measurements of the gastro-oesophageal sphincter was 0.24, and for the intragastric pH, 0.09. After peroral ingestion of 400 mg of cimetidine or placebo, simultaneous measurements of gastro-oesophageal sphincter pressure and intragastric pH were made at fixed time intervals, and at the same time blood samples were taken for determination of serum gastrin and serum cimetidine concentrations. No demonstrable difference was found in the time-course of the gastro-oesophageal sphincter pressure after ingestion of cimetidine or placebo. After ingestion of cimetidine a significant rise in intragastric pH (p less than 0.05) occurred after 40 min, and this increased pH was maintained for the remainder of the experimental period, corresponding to a serum cimetidine concentration of over 1.00 mg/l. Similarly, there was a significant rise (p less than 0.05) in serum gastrin concentration after 150 min. There was a significant direct correlation between corresponding measurements of intragastric pH and serum gastrin (p less than 0.001), between intragastric pH and serum cimetidine (p less than 0.001), and between serum gastrin and serum cimetidine (p less than 0.05). Ingestion of cimetidine results in an increase in the serum gastrin concentration in healthy subjects, presumably as a result of reduced secretion of acid in the stomach. Neither the endogenous increase in serum gastrin concentration nor the increase in intragastric pH causes alteration in the gastro-oesophageal sphincter pressure.

Adult↗
PubMed1979

Clinical and pharmacological effectiveness of cimetidine in duodenal ulcer patients.

The plasma concentration of cimetidine was measured in 40 patients with duodenal ulcer after an oral dose of 200 mg cimetidine. The peak plasma concentration was on average 1.33 mg x 1(-1) (S.D. = 0.53) and the area under the plasma concentration curve (AUC) between 60 and 120 min after cimetidine was 1.13 mg x h x 1(-1) (S.D. = 0.48). The percentage inhibition (I%) of maximal acid output (MAO) to pentagastrin during this 60-min period was 49% (S.D. = 19) with a very low, but statistically significant, correlation with the AUC, r = 0.35 (p less than 0.05), thus demonstrating a very great individual variation in sensitivity to cimetidine. In 37 of the patients the time from start of treatment with cimetidine, 1.0 g/day, to disappearance of ulcer symptoms could be assessed, and it was found that neither the individual sensitivity to cimetidine, I%/AUC, nor the gastric secretory capacity, MAO, correlated significantly with the clinical effectiveness of the cimetidine treatment, although 8 patients with a low sensitivity to cimetidine and a high MAO improved more slowly (28 days) than the other 29 patients (13 days) (p less than 0.1).

Administration, Oral↗
PubMed1978

The practical significance of nortriptyline plasma control. A prospective evaluation under routine conditions in endogenous depression.

The problem of the advantage of using nortriptyline (NT) plasma level during treatment for endogenous depression has been approached. In an ordinary psychiatric department, 34 patients had their NT level checked the second week of treatment and their dosage subsequently adjusted, if it was outside the recommended therapeutic plasma range (50--150 ng/ml). A cautious dose policy led to low plasma levels followed by dose increase in about 40% of the patients. Only in a few patients was the plasma level above the upper limit. The general outcome, about 20% failures, was compatible with the best in literature. These and other results suggest that controlling the NT plasma concentration, aiming at a level of around 100 ng/ml, might offer a therapeutic advantage, but only if the department has established a therapeutic strategy that involves such a monitoring system. The therapeutic outcome was the same as or even better in the old-age group than that in patients under 65 years of age.

Aged↗
PubMed1977

Effect of simultaneous treatment with low doses of perphenazine on plasma and urine concentrations of nortriptyline and 10-hydroxynortriptyline.

Plasma levels of nortriptyline and perphenazine were measured in six patients on continuous nortriptyline treatment before, during and after oral administration of perphenazine 4 mg t.i.d. In four patients the plasma levels of the conjugated and unconjugated principal metabolite 10-hydroxynortriptyline were also measured. Urinary excretion of conjugated and unconjugated 10-hydroxynortriptyline and plasma levels of perphenazine were determined in all six patients. During treatment with perphenazine two patients showed a slight increase in the plasma level of nortriptyline. The changes in metabolite excretion rate were inconclusive. Thus, there did not appear to be any important pharmacokinetic interaction between the two drugs at the doses used, which were normal therapeutic doses. The previously reported inhibitory effect of perphenazine on the metabolism of nortriptyline probably depended therefore, either on administration of a higher dose of perphenazine, or on treatment in the reverse sequence--a single dose of nortriptyline was given to patients already receiving perphenazine.

Adult↗
PubMed1977

Plasma concentrations of perphenazine and its sulphoxide metabolite during continuous oral treatment.

Plasma concentrations of perphenazine (PPZ) (Trilafon) and perphenazinesulphoxide (PPZSO) were estimated during a 2-week period in 16 patients receiving peroral PPZ treatment for various psychotic disorders. The results demonstrated that the average concentration of three plasma samples was a reasonably good expression of the steady-state plasma level despite a great fluctuation in the concentration from sample to sample. Increased doses in three of the patients resulted in disproportionate increases in the plasma levels. Neurological side effects were recorded and their relation to plasma concentrations are discussed.

Administration, Oral↗
PubMed1977

Mass fragmentographic quantitation of ethotoin and some of its metabolites in human urine.

A method for the determination of ethotoin and its p-hydroxylated and dealkylated metabolites in urine has been developed. Ethotoin and the metabolites were extracted from acidified urine with ethyl acetate and silylated before injection into a combined gas chromatograph--mass spectrometer. Four partly identified metabolites were recorded, but their exact quantitation was not possible as pure reference substances were not available. The limit of sensitivity was far below the amounts of ethotoin and of its metabolites found in urine from patients treated with therapeutic doses of ethotoin.

Chromatography, Gas↗